Male testosterone (T) decreases in response to childbirth. Longitudinal support for this has come from samples across cultures. In this study, we look at individual differences in this phenomenon. Utilizing a sample of U.S. fathers, we employ life history theory to investigate the influence of a father's early experience on his neuroendocrine response to fatherhood. We conducted three home visits (n = 226 fathers) from the third trimester of pregnancy to when infants were 10 months old. In this sample, T declined from the third trimester of (a partner's) pregnancy to the early months of the postnatal period. T recovered to pre-birth levels by the time infants reached 10 months old. We did not find any evidence that one's subjective experience of their early environment could account for any meaningful variability in T calibration. Objective, “event” measures of early harshness (i.e., death of a sibling/friend) and unpredictability (i.e., parent upheaval) each uniquely predicted a younger age of sexual debut. Neither harshness nor unpredictability had any (direct or indirect) effects on T calibration. Age of sexual debut did predict the rate of T recovery from 3 to 10 months postnatal. The younger one's sexual debut, the more accelerated their T ascent during this period. We discuss the potential reasons for, and implications of our mixed results.

Changes to neonatal nutrition result in long-lasting impairments in energy balance, which may be described as metabolic programing. Astrocytes, which are interconnected by gap junctions, have emerged as important players in the hypothalamic control of food intake. In order to study the effects of nutritional programming on glial morphology and protein expression, cross-fostered male Wistar rats at postnatal day 3 were assigned to three groups based on litter size: small litter (3 pups per dam, SL), normal litter (10 pups per dam, NL), and large litter (16 pups per dam, LL). Rats from the SL group exhibited higher body weight throughout the study and hyperphagia after weaning. LL animals exhibited hyperphagia, high energy efficiency and catch-up of body weight after weaning. Both the SL and LL groups at postnatal day 60 (PN60) exhibited increased levels of plasma leptin, the Lee index (as an index of obesity), adiposity content, immunoreactivity toward T-cell protein tyrosine phosphatase (TCPTP), and glial fibrillary acidic protein (GFAP) in the arcuate nucleus (ARC) of the hypothalamus. Astrocyte morphology was altered in the ARC of SL and LL animals, and this effect occurred in parallel with a reduction in immunoreactivity toward connexin 30 (CX30). The data obtained demonstrate that both neonatal over- and underfeeding promote not only alterations in the metabolic status but also morphological changes in glial cells in parallel with increasing TCPTP and changes in connexin expression.

Cultural mismatch theory suggests that a poor fit between the cultural values endorsed by individuals and the institutions to which they belong results in emotional distress and activation of physiological stress processes, particularly for underrepresented groups. To test a novel paradigm for reducing perceptions of this cultural mismatch, the current experiment evaluated whether reminding first-year Latino university students (N = 84; Mage = 18.56; SD = 0.35; 63.1% female; 85.7% Mexican descent; 65.5% first-generation college students) about institutional support for cultural diversity and inclusion would reduce neuroendocrine and affective responses to psychosocial stress. Prior to completing a modified version of the Trier Social Stress Test, participants were randomly assigned to view either a video conveying university commitment to cultural diversity and inclusion (n = 45) or a control video (n = 39) depicting a campus tour. Five saliva samples assayed for cortisol and corresponding negative affect measures were collected to assess stress reactivity and recovery patterns (pre-task baseline, post-task +30 min, +45 min, +60 min, +75 min). Repeated measures data were analyzed using bilinear spline growth models. Viewing the culture video (compared to control) significantly reduced cortisol reactivity to the TSST and post-task negative affect levels, specifically for students endorsing higher Latino cultural values (e.g., familism, respect). Post-task cortisol levels were also reduced for students endorsing higher U.S. mainstream cultural values (e.g., self-reliance, competition). Results provide novel evidence for cultural diversity in stress responsivity and individual variation in approaches to reduce perceived cultural mismatch.

Circadian (~24 h) rhythms in behavior and physiological functions are under control of an endogenous circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN directly drives some of these rhythms or serves as a coordinator of peripheral oscillators residing in other tissues and organs. Disruption of the circadian organization may contribute to disease, including stress-related disorders. Previous research indicates that the master clock in the SCN is resistant to stress, although it is unclear whether stress affects rhythmicity in other tissues, possibly mediated by glucocorticoids, released in stressful situations. In the present study, we examined the effect of uncontrollable social defeat stress and glucocorticoid hormones on the central and peripheral clocks, respectively in the SCN and liver. Transgenic PERIOD2::LUCIFERASE knock-in mice were used to assess the rhythm of the clock protein PERIOD2 (PER2) in SCN slices and liver tissue collected after 10 consecutive days of social defeat stress. The rhythmicity of PER2 expression in the SCN was not affected by stress exposure, whereas in the liver the expression showed a delayed phase in defeated compared to non-defeated control mice. In a second experiment, brain slices and liver samples were collected from transgenic mice and exposed to different doses of corticosterone. Corticosterone did not affect PER2 rhythm of the SCN samples, but caused a phase shift in PER2 expression in liver samples. This study confirms earlier findings that the SCN is resistant to stress and shows that clocks in the liver are affected by social stress, which might be due to the direct influence of glucocorticoids released from the adrenal gland.

Available pharmacotherapies to treat alcohol use disorder (AUD) show limited efficacy. Preclinical studies in mice and rats suggested that antagonists of the corticotropin releasing factor receptor 1 (CRFR1) could be more efficacious for such treatment. However, clinical trials with CRFR1 antagonists were not successful. While a number of potential explanations for this translational failure have been suggested, we hypothesized that the lack of success in clinical trials could be in part due to different neuroanatomical organization of the CRFR1 system in mice and rats versus humans. The CRF system in prairie voles (Microtus ochrogaster), a socially monogamous rodent species, also shows differences in organization from mice and rats. To test our hypothesis, we compared the efficacy of a potent CRFR1 antagonist, CP-376,395, to modulate alcohol drinking in male and female prairie voles versus male and female C57BL/6J mice using an almost identical 2-bottle choice drinking procedure. CP-376,375 (10 and 20 mg/kg, i.p.) significantly decreased alcohol intake (but not alcohol preference) in mice, but not prairie voles. Furthermore, administration of this antagonist (20 mg/kg, i.p.) prior to the partner preference test (PPT) decreased partner preference (PP) in male prairie voles. These findings support our hypothesis that the greater efficacy of CRFR1 antagonists to suppress alcohol consumption in mice and rats versus other mammalian species could be due to the differences in organization of the CRFR1 system between species. They further indicate that activity of the CRFR1 system is necessary for the formation of pair-bonds, but not consumption of high doses of alcohol. Overall, we suggest that testing potential pharmacotherapies should not rely only on studies in mice and rats.

Consumption of a high fat diet (HFD) increases circulating free fatty acids, which can enter the brain and promote a state of microgliosis, as defined by a change in microglia number and/or morphology. Most studies investigating diet-induced microgliosis have been conducted in male rodents despite well-documented sex differences in the neural control of food intake and neuroimmune signaling. This highlights the need to investigate how sex hormones may modulate the behavioral and cellular response to HFD consumption. Estradiol is of particular interest since it exerts a potent anorexigenic effect and has both anti-inflammatory and neuroprotective effects in the brain. As such, the aim of the current study was to investigate whether estradiol attenuates the development of HFD-induced microgliosis in female rats. Estradiol- and vehicle-treated ovariectomized rats were fed either a low-fat chow diet or a 60% HFD for 4 days, after which they were perfused and brain sections were processed via immunohistochemistry for microglia-specific Iba1 protein. Four days of HFD consumption promoted microgliosis, as measured via an increase in the number of microglia in the arcuate nucleus (ARC) of the hypothalamus and nucleus of the solitary tract (NTS), and a decrease in microglial branching in the ARC, NTS, lateral hypothalamus (LH), and ventromedial hypothalamus. Estradiol replacement attenuated the HFD-induced changes in microglia accumulation and morphology in the ARC, LH, and NTS. We conclude that estradiol has protective effects against HFD-induced microgliosis in a region-specific manner in hypothalamic and hindbrain areas implicated in the neural control of food intake.

Primates develop slowly relative to their body size, a pattern posited to result from ecological risk aversion. Little is known, however, about how energy balance contributes to allostatic load in juveniles. Using data collected over 8 consecutive months, we examined variation in energy balance (as measured by urinary C-peptide) and how energy balance, life history status, and social competition related to allostatic load (as measured by deviation from baseline fecal glucocorticoid metabolites, dfGCs) in 41 wild juvenile blue monkeys from 3 social groups. Juvenile energy balance was higher among females, older juveniles, when ripe fruit was more available, and when rainfall was lower. Energy balance, but not life history or competitive environments, predicted dfGC concentrations, such that juveniles generally had lower mean dfGCs when they had higher energy balance. An additional exploratory analysis of how dfGCs relate to social strategies revealed that subjects had lower dfGCs when they groomed less, and played more. Time spent grooming interacted with energy balance in predicting dfGC concentrations, so that individuals that groomed more actually had higher dfGCs when they had higher energy balance. Together these results reveal that energetic deficiencies are a true ecological risk factor in blue monkeys, and suggest that navigating the social environment via overt affiliative behavior is potentially both a stress-relieving and stress-inducing endeavor during development.

We review research supporting biological mechanisms in the development of sexual orientation. This research includes studies on neural correlates, prenatal hormones and related physical/behavioral correlates, genetics, and the fraternal birth order effect (FBOE). These studies, taken together, have provided substantial support for biological influences underlying the development of sexual orientation, but questions remain unanswered, including how biological mechanisms may differ in contributing to men's and women's sexual orientation development.

We outline the progress on the hormonal basis of human paternal behavior during the past twenty years. Advances in understanding the roles of testosterone, prolactin, oxytocin and vasopressin in fathering behavior are described, along with recent research on hormonal interactions, such as those between testosterone and cortisol, and testosterone and the peptide hormones. In addition, we briefly describe the recent leaps forward in elucidating the neurobiological and neuroendocrine basis of fatherhood, made possible by fMRI technology. Emerging from this literature is a developing and complicated story about fatherhood, highlighting the need to further understand the interplay between behavior, physiology, social context, and individual genetic variation. Given the changing roles of parents in many societies, the continued growth of this research area will provide a strong empirical knowledge base about paternal behavior on which to create policies promoting fathers' involvement in their infants' lives.

Mammals living in stable social groups often mitigate the costs of group living through the formation of social bonds and cooperative relationships. The neuropeptide hormone oxytocin (OT) is proposed to promote both bonding and cooperation although only a limited number of studies have investigated this under natural conditions. Our aim was to assess the role of OT in bonding and cooperation in male Barbary macaques (Macaca sylvanus). First, we tested for an effect of affiliation - grooming and triadic male-infant-male interactions - with bond and non-bond partners on urinary OT levels. Second, we tested whether grooming interactions (and thus increased OT levels) increase a male's general propensity to cooperate in polyadic conflicts. We collected >4000 h of behavioral data on 14 adult males and measured OT levels from 139 urine samples collected after affiliation and non-social control periods. Urinary OT levels were higher after grooming with any partner. By contrast, OT levels after male-infant-male interactions with any partner or with bond partners were not different from controls but were higher after interactions with non-bond partners. Previous grooming did not increase the likelihood of males to support others in conflicts. Collectively, our results support research indicating that OT is involved in the regulation of adult affiliative relationships. However, our male-infant-male interaction results contradict previous studies suggesting that it is affiliation with bond rather than non-bond partners that trigger the release of OT. Alternatively, OT levels were elevated prior to male-infant-male interactions thus facilitating interaction between non-bond partners. The lack of an association of grooming and subsequent support speaks against an OT linked increase in the general propensity to cooperate.

The challenge hypothesis makes specific predictions about the association between testosterone and status-seeking behaviors, but the findings linking testosterone to these behaviors are often inconsistent. The dual-hormone hypothesis was developed to help explain these inconsistencies. Specifically, according to this hypothesis, testosterone's association with status-seeking behavior depends on levels of cortisol. Here, we (1) describe the dual-hormone hypothesis in relation to the challenge hypothesis; (2) review recent studies that tested the dual-hormone hypothesis as well as meta-scientific evidence of heterogeneous dual-hormone findings across studies; (3) discuss potential explanations for this heterogeneity, including methodological considerations, contextual factors, and individual differences; and (4) provide recommendations for new work aimed at testing and extending the dual-hormone hypothesis.

Testosterone is often considered a critical regulator of aggressive behaviour. There is castration/replacement evidence that testosterone indeed drives aggression in some species, but causal evidence in humans is generally lacking and/or—for the few studies that have pharmacologically manipulated testosterone concentrations—inconsistent. More often researchers have examined differences in baseline testosterone concentrations between groups known to differ in aggressiveness (e.g., violent vs non-violent criminals) or within a given sample using a correlational approach. Nevertheless, testosterone is not static but instead fluctuates in response to cues of challenge in the environment, and these challenge-induced fluctuations may more strongly regulate situation-specific aggressive behaviour. Here, we quantitatively summarize literature from all three approaches (baseline, change, and manipulation), providing the most comprehensive meta-analysis of these testosterone-aggression associations/effects in humans to date. Baseline testosterone shared a weak but significant association with aggression (r = 0.054, 95% CIs [0.028, 0.080]), an effect that was stronger and significant in men (r = 0.071, 95% CIs [0.041, 0.101]), but not women (r = 0.002, 95% CIs [−0.041, 0.044]). Changes in T were positively correlated with aggression (r = 0.108, 95% CIs [0.041, 0.174]), an effect that was also stronger and significant in men (r = 0.162, 95% CIs [0.076, 0.246]), but not women (r = 0.010, 95% CIs [−0.090, 0.109]). The causal effects of testosterone on human aggression were weaker yet, and not statistically significant (r = 0.046, 95% CIs [−0.015, 0.108]). We discuss the multiple moderators identified here (e.g., offender status of samples, sex) and elsewhere that may explain these generally weak effects. We also offer suggestions regarding methodology and sample sizes to best capture these associations in future work.

The investigation of hormones, brain function and behavior over the past 50 years has played a major role in elucidating how the brain and body communicate reciprocally via hormones and other mediators and how this impacts brain and body health both positively and negatively. This is illustrated here for the hippocampus, a uniquely sensitive and vulnerable brain region, study of which as a hormone target has provided a gateway into the rest of the brain. Hormone actions on the brain and hormones generated within the brain are now recognized to include not only steroid hormones but also metabolic hormones and chemical signals from bone and muscle. Moreover, steroid hormones, and some metabolic hormones, and their receptors, are generated by the brain for specific functions that synergize with effects of those circulating hormones. Hormone actions in hippocampus have revealed its capacity, and that of other brain regions, for adaptive plasticity, loss of which needs external intervention in, for example, mood disorders. Early life experiences as well as in utero and transgenerational effects are now appreciated for their lasting effects at the level of gene expression affecting the capacity for adaptive plasticity. Moreover sex differences are recognized as affecting the whole brain via both genetic and epigenetic mechanisms. The demonstrated plasticity of a healthy brain gives hope that interventions throughout the life course can ameliorate negative effects by reactivating that plasticity and the underlying epigenetic activity to produce compensatory changes in the brain with more positive consequences for the body.

There is increasing evidence that reproductive hormones exert regulatory effects in the central nervous system that can influence behavioral, cognitive, perceptual, affective, and motivational processes. These effects occur in adults and post-pubertal individuals, and can be demonstrated in humans as well as laboratory animals. Large changes in 17β-estradiol and progesterone occur over the ovarian cycle (i.e., the menstrual cycle) and afford a way for researchers to explore the central nervous system (CNS) effects of these hormones under natural physiological conditions. Increasingly, oral contraceptives are also being studied, both as another route to understanding the CNS effects of reproductive hormones and also as pharmacological agents in their own right. This mini-review will summarize the basic physiology of the menstrual cycle and essential facts about oral contraceptives to help novice researchers to use both paradigms effectively.

A growing body of research suggests that hormonal contraceptive (HC) use may be associated with lower self-control, as well as structural and functional differences in women's brains that could contribute to differences in perseverance on tasks requiring cognitive control. Here, we sought to extend this research by examining the relationship between HC use and college-aged women's perseverance (i.e., time spent) and performance on tasks requiring cognitive control. Across two studies, we find that, compared to naturally-cycling women, women using HCs display less perseverance on both simple (i.e., a spot-the-difference game) and challenging (i.e., Graduate Record Examination quantitative problems) tasks. Moreover, these differences in perseverance were found to predict performance decrements across tasks, with women taking HCs performing worse because they spent less time on the tasks. By demonstrating how HC use may influence perseverance and thereby performance, these results contribute to a growing body of research examining the unintended implications of HC use on cognition, learning, and memory.

The majority of HIV+ patients present with neuroendocrine dysfunction and ~50% experience co-morbid neurological symptoms including motor, affective, and cognitive dysfunction, collectively termed neuroHIV. In preclinical models, the neurotoxic HIV-1 regulatory protein, trans-activator of transcription (Tat), promotes neuroHIV pathology that can be exacerbated by opioids. We and others find gonadal steroids, estradiol (E2) or progesterone (P4), to rescue Tat-mediated pathology. However, the combined effects of Tat and opioids on neuroendocrine function and the subsequent ameliorative capacity of gonadal steroids are unknown. We found that conditional HIV-1 Tat expression in naturally-cycling transgenic mice dose-dependently potentiated oxycodone-mediated psychomotor behavior. Tat increased depression-like behavior in a tail-suspension test among proestrous mice, but decreased it among diestrous mice (who already demonstrated greater depression-like behavior); oxycodone reversed these effects. Combined Tat and oxycodone produced apparent behavioral disinhibition of anxiety-like responding which was greater on diestrus than on proestrus. These mice made more central entries in an open field, but spent less time there and demonstrated greater circulating corticosterone. Tat increased the E2:P4 ratio of circulating steroids on diestrus and acute oxycodone attenuated this effect, but repeated oxycodone exacerbated it. Corticotropin-releasing factor was increased by Tat expression, acute oxycodone exposure, and was greater on diestrus compared to proestrus. In human neuroblastoma cells, Tat exerted neurotoxicity that was ameliorated by E2 (1 or 10 nM) or P4 (100, but not 10 nM) independent of oxycodone. Oxycodone decreased gene expression of estrogen and κ-opioid receptors. Thus, neuroendocrine function may be an important target for HIV-1 Tat/opioid interactions.

Male Syrian hamsters (Mesocricetus auratus) administered anabolic/androgenic steroids during adolescent development display increased aggression and decreased anxious behavior during the adolescent exposure period. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts and hamsters exhibit decreased aggression and increased anxious behavior. This study investigated the hypothesis that alterations in anterior hypothalamic signaling through serotonin type-3 receptors modulate the behavioral shift between adolescent anabolic/androgenic steroid-induced aggressive and anxious behaviors during the withdrawal period. To test this, hamsters were administered anabolic/androgenic steroids during adolescence then withdrawn from drug exposure for 21 days and tested for aggressive and anxious behaviors following direct pharmacological manipulation of serotonin type-3 receptor signaling within the latero-anterior hypothalamus. Blockade of latero-anterior hypothalamic serotonin type-3 receptors both increased aggression and decreased anxious behavior in steroid-treated hamsters, effectively reversing the pattern of behavioral responding normally observed during anabolic/androgenic steroid withdrawal. These findings suggest that the state of serotonin neural signaling within the latero-anterior hypothalamus plays an important role in behavioral shifting between aggressive and anxious behaviors following adolescent exposure to anabolic/androgenic steroids.

Our review focuses on findings from mammals as part of a Special Issue “30th Anniversary of the Challenge Hypothesis”. Here we put forth an integration of the mechanisms through which testosterone controls territorial behavior and consider how reproductive experience may alter these mechanisms. The emphasis is placed on the function of socially induced increases in testosterone (T) pulses, which occur in response to social interactions, as elegantly developed by Wingfield and colleagues. We focus on findings from the monogamous California mouse, as data from this species shows that reproductive status is a key factor influencing social interactions, site fidelity, and vigilance for offspring defense. Specifically, we examine differences in T pulses in sexually naïve versus sexually experienced pair bonded males. Testosterone pulses influence processes such as social decision making, the winner-challenge effect, and location preferences through rewarding effects of T. We also consider how social and predatory vigilance contribute to T pulses and how these interactions contribute to a territory centered around maximizing reproduction. Possible underlying mechanisms for these effects include the nucleus accumbens (rewarding effects of testosterone), hippocampus (spatial memories for territories), and the bed nucleus of the stria terminalis (social vigilance). The development of the challenge effect has provided an ideal framework for understanding the complex network of behavioral, environmental, physiological and neural mechanisms that ultimately relates to competition and territoriality across taxa. The opportunity to merge research on the challenge effect using both laboratory and field research to understand social behavior is unparalleled.

Androgens, traditionally viewed as hormones that regulate secondary sexual characteristics and reproduction in male vertebrates, are often modulated by social stimuli. High levels of the ‘social hormone’ testosterone (T) are linked to aggression, dominance, and competition. Low T levels, in contrast, promote sociopositive behaviours such as affiliation, social tolerance, and cooperation, which can be crucial for group-level, collective behaviours. Here, we test the hypothesis that - in a collective context - low T levels should be favourable, using non-reproductive male and female stickleback fish (Gasterosteus aculeatus) and non-invasive waterborne hormone analysis. In line with our predictions, we show that the fishes' T levels were significantly lower during shoaling compared to when alone, with high-T individuals showing the largest decrease. Ruling out stress-induced T suppression and increased T conversion into oestradiol, we find evidence that shoaling directly affects androgen responsiveness. We also show that groups characterized by lower mean T exhibit less hierarchical leader-follower dynamics, suggesting that low T promotes egalitarianism. Overall, we show that collective action results in lower T levels, which may serve to promote coordination and group performance. Our study, together with recent complementary findings in humans, emphasizes the importance of low T for the expression of sociopositive behaviour across vertebrates, suggesting similarities in endocrine mechanisms.

E2 and its alpha receptor (ERα) have an essential role in the regulation of maternal behavior. In dwarf hamster (Phodopus campbelli), E2 facilitates the display of paternal care, and it is possible that ERα is part of the neuroendocrine mechanisms that regulate this behavior. The aim of this study was to analyze the influence of copulation, cohabitation with the pregnant mate and the presence of the pups on paternal behavior, circulating E2 levels and the presence of ERα in the medial preoptic area (mPOA) and medial amygdala (MeA) in dwarf hamsters. Eight males were mated with intact females (IFs), 8 with tubally ligated females (TLFs) and 8 with ovariectomized females (OFs). In males mated with IFs, paternal behavior tests were performed after copulation, halfway through pregnancy and 24 h after the birth of their pups. Males mated with TLFs were subjected to paternal behavior tests at equivalent periods as the males mated with IFs. In males mated with OFs, paternal behavior tests were performed on days 1, 5 and 10 of cohabitation. After the last paternal behavior tests, blood samples were taken for quantification of E2 by radioimmunoassay (RIA), and the brains were dissected to determine ERα immunoreactivity (ir) in the mPOA and MeA. Fathers mated with IFs had higher serum E2 concentrations and more ERα-ir cells in the mPOA than those of males mated with TLFs and OFs. These results suggest that E2 and its ERα may be associated with paternity in the dwarf hamster.

Phytoestrogens comprise biologically active constituents of human and animal diet that can impact on systemic and local estrogen functions in the brain. Here we report on the importance of dietary phytoestrogens for maintaining activity in a brain circuit controlling aggressive and social behavior of male mice. After six weeks of low-phytoestrogen chronic diet (diadzein plus genistein <20 μg/g) a reduction of intermale aggression and altered territorial marking behavior could be observed, compared to littermates on a standard soy-bean based diet (300 μg/g). Further, mice on low-phyto diet displayed a decrease in sociability and a reduced preference for social odors, indicating a general disturbance of social behavior. Underlying circuits were investigated by analysing the induction of the activity marker c-Fos upon social encounter. Low-phyto diet led to a markedly reduced c-Fos induction in the medial as well as the cortical amygdala, the lateral septum, medial preoptic area and bed nucleus of the stria terminalis. No difference between groups was observed in the olfactory bulb. Together our data suggest that dietary phytoestrogens critically modulate social behavior circuits in the male mouse brain.

Empathy is a cornerstone of human sociality. It has important consequences for our interpersonal relationships and for navigating our social world more generally. Although research has identified numerous psychological factors that can influence empathy, evidence suggests that empathy may also be rooted in our biology and, in particular, the gonadal steroid hormone testosterone. To date, much of the research linking testosterone and empathy has focused on the 2D:4D ratio (i.e., the ratio of the lengths of the index and ring fingers), and the results have been mixed. These mixed results, however, may be due to reliance on self-report measures to assess empathy, which can be vulnerable to self-presentation, as well as social-cultural norms about gender/sex differences in empathy. Moreover, although some have argued that digit ratio is an indicator of prenatal androgen exposure, the evidence for this to date is weak. Here, we aimed to follow up on this prior work, using a naturalistic empathic accuracy task in which participants dynamically track, in real-time, the emotional state of targets. We show that lower digit ratio (Study 1; N = 107) and higher circulating testosterone (Study 2; N = 76) are associated with poorer empathic accuracy performance; critically, these effects hold when controlling for sex/gender. In neither study, however, did we find effects on self-reported empathy. Our results highlight the limitations of self-report measures and support the notion that endogenous testosterone levels as well as 2D:4D ratio are related to key social-cognitive competencies like empathic accuracy.

The estrogen receptor (ER) mechanisms by which 17β-estradiol influences depressive-like behaviour have primarily been investigated acutely and not within an animal model of depression. Therefore, the current study aimed to dissect the contribution of ERα and ERβ to the effects of 17β-estradiol under non-stress and chronic stress conditions. Ovariectomized (OVX) or sham-operated mice were treated chronically (47 days) with 17β-estradiol (E2), the ERβ agonist diarylpropionitrile (DPN), the ERα agonist propylpyrazole-triol (PPT), or vehicle. On day 15 of treatment, mice from each group were assigned to chronic unpredictable stress (CUS; 28 days) or non-CUS conditions. Mice were assessed for anxiety- and depressive-like behaviour and hypothalamic-pituitary-adrenal (HPA) axis function. Cytokine and chemokine levels, and postsynaptic density protein 95 were measured in the hippocampus and frontal cortex, and adult hippocampal neurogenesis was assessed. Overall, the effects of CUS were more robust that those of estrogenic treatments, as seen by increased immobility in the tail suspension test (TST), reduced PSD-95 expression, reduced neurogenesis in the ventral hippocampus, and HPA axis negative feedback dysregulation. However, we also observe CUS-dependent and -independent effects of ovarian status and estrogenic treatments. The effects of CUS on PSD-95 expression, the cytokine milieu, and in TST were largely driven by PPT and DPN, indicating that these treatments were not protective. Independent of CUS, estradiol increased neurogenesis in the dorsal hippocampus, blunted the corticosterone response to an acute stressor, and increased anxiety-like behaviour. These findings provide insights into the complexities of estrogen signaling in modulating depressive-like phenotypes under non-stress and chronic stress conditions.

Relatively little is known about the effects of endogenous and exogenous steroid hormones on ecologically relevant behavioral and cognitive phenotypes in women, such as emotion recognition, despite the widespread use of steroid hormone-altering hormonal contraceptives (HCs). Though some previous studies have examined the effect of HC use, estradiol, progesterone, and testosterone on emotion recognition in women, they have been limited by cross-sectional designs, small sample sizes (total n < 100), and compromised statistical power to detect significant effects. Using data from two test sessions in a large sample of naturally cycling women (NC; n = 192) and women on HCs (n = 203), we found no group differences in emotion recognition; further, the lack of group differences in emotion recognition was not modulated by item difficulty or emotional valence. Among NC women who provided saliva samples across two sessions that were assayed for estradiol and progesterone concentrations, we found no compelling evidence across models that between-subject differences and within-subject fluctuations in these ovarian hormones predicted emotion recognition accuracy, with the exception that between-subjects estradiol negatively predicted emotion recognition for emotions of neutral valence (p = .042). Among HC women who provided saliva samples across two sessions that were assayed for testosterone, we found no compelling evidence that between-subjects differences and within-subject fluctuations in testosterone predicted emotion recognition accuracy. Overall, our analyses provide little support for the idea that circulating endogenous or exogenous ovarian hormones influence emotion recognition in women.

The hormonal milieu that exists during reproduction is one of the key factors influencing the trade-off between reproductive investment and self-maintenance. Much previous work in birds has focused on prolactin as a physiological mediator since prolactin is involved in the onset and maintenance of parental care. However, how prolactin relates to reproductive success in terms of altering parental behavior in wild bird populations is not fully understood. Here, we report prolactin concentrations in breeding Kentish plovers (Charadrius alexandrinus), a small shorebird with variable mating systems and parental care, as an ecological model of mating system evolution. Throughout the breeding season, we estimated the circulating prolactin concentrations in male and female plovers during incubation. In addition, we monitored parental behavior and determined the fate of nests. We found that prolactin concentrations decreased during incubation but increased with clutch completion date. In addition, males and females with high prolactin concentrations spent more time on incubation than those with low prolactin concentrations. Importantly, higher prolactin concentrations in either males or females predict higher nest survival. Our results suggest that prolactin is an indicator of parental behavior in a wild shorebird population, although additional studies including experimental manipulation of prolactin concentrations are necessary to verify this relationship.

Social behavior plays a significant role in the formation of social structure and population regulation in both animals and humans. Oxytocin (OXT) and its receptor (OXTR) are well known for regulating social behaviors, but their upstream regulating factors are rarely investigated. We hypothesized that the phosphorylation of the signal transducer and activator of transcription 3 (p-Stat3) may regulate social and aggressive behaviors via the OXT system in the nucleus accumbens (NAc). To test this hypothesis, OXT, p-Stat3 inhibitor, OXTR antagonist, and OXT plus p-Stat3 inhibitor were infused, respectively, into the NAc in the brain of male Brandt's voles (Lasiopodomys brandtii) – a social rodent species in grassland of Inner Mongolia, China. Our data showed that blockage of p-Stat3-Tyr705 signaling pathway in the NAc not only increased aggressive behavior but also impaired social recognition of male Brandt's voles via its effects on the expression of local OXT and OXTR. These results have illustrated a novel signaling pathway of p-Stat3-Tyr705 in regulating social behaviors via the OXT system.

Circulating levels of testosterone have been positively associated with impulsivity. The present study investigates the effect of testosterone administration on impulsivity in an intertemporal choice task, where participants are given a choice between smaller-sooner rewards and larger-later rewards. Healthy young male participants (n = 111) received a single-dose of 150 mg testosterone gel in a double-blind, placebo-controlled, between-subjects design. At 180 min post-administration, participants performed the decision-making task. Both model-free (i.e., higher indifference point) and model-based (i.e., steeper discounting rate) parameters revealed that testosterone administration increased impulsive choice. This finding supports the hypothesis that exogenous testosterone increases impulsivity among healthy young males in a laboratory task.

Alzheimer's disease (AD) is a neurodegenerative disease that severely affects the health and lifespan of the elderly worldwide. Recently, the correlation between AD and type 2 diabetes mellitus (T2DM) has received intensive attention, and a promising new anti-AD strategy is the use of anti-diabetic drugs. Oxyntomodulin (Oxm) is a peptide hormone and growth factor that acts on neurons in the hypothalamus. OXM activates glucagon-like peptide 1 (GLP-1) and glucagon (Gcg) receptors, facilitates insulin signaling and has neuroprotective effects against Aβ1–42-induced cytotoxicity in primary hippocampal neurons. Here, we tested the effects of the protease-resistant analogue (D-Ser2)Oxm on spatial memory and synaptic plasticity and the underlying molecular mechanisms in the APP/PS1 transgenic mouse model of AD. The results showed that (D-Ser2)Oxm not only alleviated the impairments of working memory and long-term spatial memory, but also reduced the number of Aβ plaques in the hippocampus, and reversed the suppression of hippocampal synaptic long-term potentiation (LTP). Moreover, (D-Ser2)Oxm administration significantly increased p-PI3K/p-AKT1 expression and decreased p-GSK3β levels in the hippocampus. These results are the first to show an in vivo neuroprotective role of (D-Ser2)Oxm in APP/PS1 mice, and this role involves the improvement of synaptic plasticity, clearance of Aβ and normalization of PI3K/AKT/GSK3β cell signaling in the hippocampus. This study suggests that (D-Ser2)Oxm holds promise for the prevention and treatment of AD.

As a derivative of testosterone, androstadienone (AND) can influence human psychological and physiological states. To explore the influence of AND on women's preferences for male sexual dimorphic faces in a mate-choice context, we asked 52 females in the luteal phase to choose one from four sexual dimorphic male faces in a long-term and short-term context while inhaling 250 μm of AND or a placebo odor on two consecutive days. Results revealed that participants had a greater and lesser preference for the +30% masculinized and 60% feminized faces, respectively, while inhaling AND, as compared to when inhaling the placebo. The AND intervention resulted in a rightward shift of the women's preference for male sexual dimorphic faces across the continuum of femininity-masculinity. The current findings highlight that AND may influence women's preference for male sexually dimorphic faces in a mate-choice context.

In animals, the expression of diverse reproductive behaviors is hormonally regulated. In particular, vocalizing during courtship has been related to circulating androgen levels, and reciprocally, conspecific vocalizations are known to modulate androgen secretion in vertebrates. The effect of natural sounds of abiotic origin on hormonal status has virtually not received attention. Therefore, we evaluated the vocal responses of male Batrachyla taeniata frogs to conspecific chorus and rainfall sounds in natural and controlled laboratory settings, measuring the testosterone levels of exposed individuals. In field and laboratory conditions, testosterone levels of frogs exposed to 31.5 min of chorus and rain sounds and non-exposed individuals were similar. In the field, frogs increased their call rate in response to playbacks of chorus and rain sound, but the evoked calling activity was unrelated to plasma testosterone. In contrast to the field, frogs showed limited responsiveness to 31.5-min acoustic exposures in the laboratory. Similarly to the field, for vocally active males tested in the laboratory there was no association between call rate and testosterone levels. Additionally, in this group, testosterone levels were higher in vocally active males relative to non-calling individuals. Overall, these results indicate that in B. taeniata testosterone levels are not altered following a short-term exposure to conspecific biotic and to abiotic sounds. Our results are suggestive of a threshold influence of testosterone on the vocal activity of the species studied. Further explorations of the influence of abiotic sounds on endocrine activation are required to understand how animals respond to variable acoustic environmental conditions.

In this paper I discuss how the challenge hypothesis (Wingfield et al., 1990) influenced the development of ideas about animal personality, and describe particularly promising areas for future study at the intersection of these two topics. I argue that the challenge hypothesis influenced the study of animal personality in at least three specific ways. First, the challenge hypothesis drew attention to the ways in which the environment experienced by an organism – including the social environment – can influence biological processes internal to the organism, e.g. changes to physiology, gene expression, neuroendocrine state and epigenetic modifications. That is, the challenge hypothesis illustrated the bidirectional, dynamic relationship between hormones and (social) environments, thereby helping us to understand how behavioral variation among individuals can emerge over time. Because the paper was inspired by data collected on free living animals in natural populations, it drew behavioral ecologists' attention to this phenomenon. Second, the challenge hypothesis highlighted what became a paradigmatic example of a hormonal mechanism for a behavioral spillover, i.e. testosterone's pleiotropic effects on both territorial aggression and parental care causes aggression to “spillover” to influence parenting behavior, thereby limiting behavioral plasticity. Third, the challenge hypothesis contributed to what is now a cottage industry examining individual differences in hormone titres and their relationship with behavioral variation. I argue that one particularly promising future research direction in this area is to consider the active role of behavior and behavioral types in eliciting social interactions, including territorial challenges.

According to the Challenge Hypothesis, social interactions, particularly among males, have a strong influence on circulating androgen levels. Specifically, males should respond to social challenges from conspecific males with a rapid increase in plasma androgen levels which support and stimulate further aggression. This basic tenet of the Challenge Hypothesis, an androgen increase in response to a social challenge from another male, has been tested in all vertebrate classes. While early studies generally supported the Challenge Hypothesis, more recent work has noted numerous exceptions, particularly in birds. Here, we conduct a meta-analysis of studies in fish, amphibians, non-avian reptiles, and mammals that test the prediction that circulating androgen levels of males should increase in response to an experimental challenge from another male. We found that teleost fish often increase androgens during such challenges, but other vertebrate groups show more mixed results. Why should fish be different from the other taxa? In fish with paternal care of young, the potential conflict between mating, being aggressive towards other males, and taking care of offspring is alleviated, because females typically choose males based on their defense of an already existing nest. Hence, rather than regulating the trade-off between mating, aggression, and parenting, androgens may have been co-opted to promote all three behaviors. For other taxa, increasing androgen levels only makes sense when the increase directly enhances reproductive success. Thus, the increase in androgen levels is a response to mating opportunities rather than a response to challenge from another male. To further our understanding of the role of a change in androgen levels in mediating behavioral decision-making between mating, aggression, and parenting, we need studies that address the behavioral consequences of an increase in androgens after male-male encounters and studies that test the androgen responsiveness of species that differ in the degree of paternal care.

The Challenge Hypothesis (Wingfield et al., 1990) originally focused on adult male avian testosterone elevated in response to same-sex competition in reproductive contexts. The purpose of the present paper is to demonstrate how the Challenge Hypothesis has shaped ideas about human life histories. We conduct a citation analysis, drawing upon 400 Google Scholar citations in the human literature to identify patterns in this body of scholarship. We cover key factors, such as context and personality traits, that help explain variable testosterone responses such as winning/losing to adult competitive behavior. Findings from studies on courtship and sexual behavior indicate some variation in testosterone responses depending on factors such as motivation. A large body of research indicates that male testosterone levels are often lower in contexts of long-term committed partnerships and nurturant fathering and aligned with variation in male mating and parenting effort. As the Challenge Hypothesis is extended across the life course, DHEA and androstenedione (rather than testosterone) appear more responsive to juvenile male competitive behavior, and during reproductive senescence, baseline male testosterone levels decrease just as male life history allocations show decreased mating effort. We discuss how research on testosterone administration, particularly in older men, provides causal insight into effects of testosterone in humans, and how this “natural experiment” can be viewed in light of the Challenge Hypothesis. We synthesize central concepts and findings, such as an expanded array of costs of testosterone that inform life history tradeoffs between maintenance and reproductive effort, and we conclude with directions for future research.

Exhibiting behavioral plasticity in order to mount appropriate responses to dynamic and novel social environments is crucial to the survival of all animals. Thus, how animals regulate flexibility in the timing, duration, and intensity of specific behaviors is of great interest to biologists. In this review, we discuss how animals rapidly respond to social challenges, with a particular focus on aggression. We utilize a conceptual framework to understand the neural mechanisms of aggression that is grounded in Wingfield and colleagues' Challenge Hypothesis, which has profoundly influenced how scientists think about aggression and the mechanisms that allow animals to exhibit flexible responses to social instability. Because aggressive behavior is rooted in social interactions, we propose that mechanisms modulating prosocial behavior may be intricately tied to mechanisms of aggression. Therefore, in order to better understand how aggressive behavior is mediated, we draw on perspectives from social neuroscience and discuss how social context, species-typical behavioral phenotype, and neural systems commonly studied in relation to prosocial behavior (i.e., neuropeptides) contribute to organizing rapid responses to social challenges. Because complex behaviors are not the result of one mechanism or a single neural system, we consider how multiple neural systems important for prosocial and aggressive behavior (i.e., neuropeptides and neurosteroids) interact in the brain to produce behavior in a rapid, context-appropriate manner. Applying a systems neuroscience perspective and seeking to understand how multiple systems functionally integrate to rapidly modulate behavior holds great promise for expanding our knowledge of the mechanisms underlying social behavioral plasticity.

Oxytocin (OXT) regulates adult social behavior and has been implicated in its development. Because mammalian milk contains OXT and we have recently identified OXT receptors (OXTR) in the face and oronasal cavity of pre-weaning mice, we hypothesize that orally applied OXT may impact brain activity and acute behavior in developing mice. Oral OXT may have effects in the absence of sensory stimulation or perhaps by modulating sensory input, such as whisker stimulation. The present study investigates the acute c-Fos response in the paraventricular nucleus of the hypothalamus (PVN) and along whisker sensory processing brain regions (trigeminothalamocortical circuit) to orally applied OXT, compared to saline, with and without whisker stimulation in postnatal day (P) 14 and P21 male and female mice. Acute behavioral responses were also quantified after oral OXT with whisker stimulation in a non-social context. Oral OXT with and without whisker stimulation increased c-Fos activity in the PVN of males and decreased c-Fos in the ventroposterior medial thalamus in both males and females compared to saline. Additionally, oral OXT with whisker stimulation decreased c-Fos activity across whisker sensory processing brain regions in males and females and decreased c-Fos activity in the trigeminal motor nucleus of females. Lastly, oral OXT with whisker stimulation increased males' locomotor behavior and decreased females' oromotor behavior compared to saline-treated controls. These data indicate that orally applied OXT has acute brain and behavioral effects on developing mice. OXT-modulated sensory signals may bias brain and behavior development toward the social world.

Alzheimer's disease and other forms of cognitive decline are significantly more prevalent in post-menopausal women. Decreased estrogen levels, due to menopause or ovariectomy, may contribute to memory impairments and neurodegeneration. Another result of decreased estrogen levels is elevated luteinizing hormone (LH). Elevated LH after menopause/ovariectomy has been shown to impair cognition in both human and animal studies. Lowering LH levels rescues spatial memory in ovariectomized (ovx) rodents, yet the mechanisms of these effects are still unclear. Estrogens appear to exert some of their effects on memory by increasing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. In these studies, we explored whether lowering LH may act by increasing BDNF. Ovx rats were treated with Antide, a gonadotropin releasing hormone receptor antagonist that lowers LH levels, or with estradiol. Both Antide and estradiol treatment enhanced spatial memory in ovx females. Both were found to be ineffective when a BDNF receptor antagonist was administered. Immunohistochemical analysis revealed that both Antide and estradiol increased BDNF expression in the hippocampus. Dendritic spine density on pyramidal cells in CA1 was unchanged by any treatment. These results provide evidence for a relationship between LH and BDNF in the hippocampus and demonstrate that estrogen-increasing and LH-lowering treatments may both require BDNF signaling in order to improve spatial memory.

Temperate zone songbird species, such as the canary (Serinus canaria), can serve as model systems to investigate adult seasonal plasticity in brain and behavior. An increase in day length, experienced by canaries in the early spring stimulates gonadal recrudescence and an associated increase in circulating testosterone concentrations. This increase in plasma testosterone results in marked morphological changes in well-defined neural circuitry regulating reproductive behaviors including birdsong as well as behavioral changes such as increases in song length and complexity. An obvious measure of plasticity in neural morphology can be assessed via changes in brain nuclei volume and testosterone actions on a number of cellular features including the integration and incorporation of new neurons in the adult canary brain. Previous work in our lab suggests that there may be systematic intraspecific variability within canaries in testosterone-induced adult neuroplasticity. For example, the song nucleus HVC increases in size in response to testosterone in male canaries but we found that males of the American Singer strain exhibited minimal and variable responses as compared to other canary strains such as the Border canary strain, which is thought to be closer to wild type canaries. In this study, we systematically compared the effects of testosterone on the volume of song nuclei and the number of new neurons as assessed with the neurogenesis marker doublecortin in American Singer and Border canaries. We found more pronounced testosterone-induced neuroplasticity in the Border strain than the American Singer. These data suggest that the process of selection for certain strain phenotypes is also associated with significant changes in hormone-regulated brain plasticity.

Background The hypothalamic-pituitary-adrenal (HPA) axis is the main neuroendocrine system that controls stress responses, including fear learning. To further understand the correlation between the HPA axis and stress- and fear-related symptoms in humans, the current study investigated the relationship between HPA axis gene polymorphisms and a stress- and fear-related disorder, posttraumatic stress disorder (PTSD). This is the first study that systematically investigates the correlations between HPA axis genes and distinct PTSD symptom clusters. Methods Participants included 1132 Chinese earthquake survivors (772 women and 360 men). PTSD symptoms were measured by the PTSD Checklist for DSM-5 (PCL-5), and the severity (total symptoms) and symptom clusters were calculated according to the hybrid seven-factor model of DSM-5 PTSD. We genotyped eight single nucleotide polymorphisms (SNPs) of three HPA axis genes, including FKBP5, CRHR1 and CRHR2. Results The main effects of the CRHR2 SNP rs2267715 were associated with PTSD severity (P = 0.0035) and all PTSD symptom clusters except dysphoric arousal (P ranging from 0.0011 to 0.048). In women, a gene–environment interaction (G × E) effect of FKBP5 (rs3800373 × trauma exposure) was correlated with PTSD severity (P = 0.038), externalizing behaviors, anxious arousal and dysphoric arousal symptoms (P ranging from 0.014 to 0.028); the G × E effect of CRHR1 (rs4458044 × trauma exposure) was associated with anxious arousal symptoms (P = 0.016). In men, a gene–gene interaction (G × G) effect of FKBP5–CRHR1 (rs9470080 × rs4458044) was associated with PTSD severity (P = 0.0091), intrusion, negative affect, externalizing behaviors and anxious arousal (P ranging 0.012–0.049). Conclusion Our results systematically revealed that the main effects and G × E and G × G effects of some genetic polymorphisms of HPA axis genes are involved in the severity and distinct symptom clusters of PTSD.

Early-life stress exposure can confer vulnerability for development of psychiatric illnesses and impaired cognition in adulthood. It is well-known that early-life stress can dysregulate the hypothalamic-pituitary-adrenal (HPA) axis in a sex-dependent manner. Specifically, uniparental rodent models of prolonged disrupted mother-offspring relationships (e.g., maternal separation) have demonstrated greater alterations in stress responsivity in adult males, compared to females. Also, chronic early-life stressors (e.g., limited bedding model) impair cognitive function in males more than females. However, the sex-dependent effects of early-life stress and later-life chronic HPA axis activation on cognition have not been well-characterized. Here, we utilized the biparental California mouse (Peromyscus californicus) to model the early-life adversity of paternal deprivation (PD). Fathers either remained in the nest (biparental care) or were permanently removed (PD) on postnatal day (PND) 1. Adult offspring were exposed to daily handling (control) or chronic variable stress (CVS; three stressors for seven days). Twenty-four hours after the final stressor, the novel object recognition (NOR) task commenced, followed by serum collection for corticosterone (CORT) analysis. Independent of sex or rearing, CVS increased CORT. Exploration during acquisition for the NOR task was increased as a result of CVS and PD. During NOR testing, non-stressed females exhibited greater difference scores (i.e., increased recognition memory), compared to non-stressed males. However, the addition of CVS diminished difference scores in females – an effect not observed in CVS-exposed males. Overall, these data suggest that neonatal paternal experience, sex, and chronic stress contribute to exploratory behavior, cognition, and stress hormone concentrations in a biparental species.

The objective of this study was to investigate the role of palmitoylethanolamide (PEA) in the regulation of energy homeostasis in goldfish (Carassius auratus). We examined the effects of acute or chronic intraperitoneal treatment with PEA (20 μg·g−1 body weight) on parameters related to food intake and its regulatory mechanisms, locomotor activity, glucose and lipid metabolism, and the possible involvement of transcription factors and clock genes on metabolic changes in the liver. Acute PEA treatment induced a decrease in food intake at 6 and 8 h post-injection, comparable to that observed in mammals. This PEA anorectic effect in goldfish could be mediated through interactions with leptin and NPY, as PEA increased hepatic expression of leptin aI and reduced hypothalamic expression of npy. The PEA chronic treatment reduced weight gain, growth rate, and locomotor activity. The rise in glycolytic potential together with the increased potential of glucose to be transported into liver suggests an enhanced use of glucose in the liver after PEA treatment. In addition, part of glucose may be exported to be used in other tissues. The activity of fatty acid synthase (FAS) increased after chronic PEA treatment, suggesting an increase in the hepatic lipogenic capacity, in contrast with the mammalian model. Such lipogenic increment could be linked with the PEA-induction of REV-ERBα and BMAL1 found after the chronic treatment. As a whole, the present study shows the actions of PEA in several compartments related to energy homeostasis and feeding behavior, supporting a regulatory role for this N-acylethanolamine in fish.

Oxytocin and testosterone coordinate adaptive social behaviors with stimuli in the environment. Administration of oxytocin and testosterone is associated with increased and reduced indicators of empathy, respectively, but how levels of these hormones are jointly affected by naturalistic empathy-inducing stimuli remains unclear. In this study, salivary oxytocin and testosterone levels were measured in 173 healthy adults before and after watching a video involving a gravely ill child. Participants also completed questionnaires to assess psychological variables predicted to affect oxytocin reactivity (Autism-Spectrum Quotient, Interpersonal Reactivity Index, Empathy and Systemizing Quotients). On average, there was a 14% increase in oxytocin (p = 0.003) and 4% decrease in testosterone (p = 0.001) pre- to post-video. Opposite directional changes in hormone levels occurred together, as supported by a chi-square test (p < 0.001) and a circular statistics test (p < 0.05). Considered separately, psychological traits did not predict hormone levels or changes to any appreciable degree. However, oxytocin and testosterone changes were linked with empathy relative to systemizing such that: (1) ‘Empathy Bias’ was associated with a large oxytocin increase but little change in testosterone, while (2) ‘Systemizing Bias’ and ‘Balance’ between empathy and systemizing were associated with a decrease in testosterone but little change in oxytocin. These findings suggest that participants were divisible into ‘high oxytocin responders’ (relatively empathetic) and ‘high testosterone responders’ (balanced or systemizing-biased). These findings support a model of joint, opposite changes in oxytocin and testosterone under experimental empathy induction, with high, somewhat predictable, diversity in individual responses.

Low frequency components (i.e. a low pitch (F0) and low formant spacing (ΔF)) signal high salivary testosterone and height in adult male voices and are associated with high masculinity attributions by unfamiliar listeners (in both men and women). However, the relation between the physiological, acoustic and perceptual dimensions of speakers' masculinity prior to puberty remains unknown. In this study, 110 pre-pubertal children (58 girls), aged 3 to 10, were recorded as they described a cartoon picture. 315 adults (182 women) rated children's perceived masculinity from the voice only after listening to the speakers' audio recordings. On the basis of their voices alone, boys who had higher salivary testosterone levels were rated as more masculine and the relation between testosterone and perceived masculinity was partially mediated by F0. The voices of taller boys were also rated as more masculine, but the relation between height and perceived masculinity was not mediated by the considered acoustic parameters, indicating that acoustic cues other than F0 and ΔF may signal stature. Both boys and girls who had lower F0, were also rated as more masculine, while ΔF did not affect ratings. These findings highlight the interdependence of physiological, acoustic and perceptual dimensions, and suggest that inter-individual variation in male voices, particularly F0, may advertise hormonal masculinity from a very early age.

Females of many northern temperate songbird species sing sporadically. However, detailed descriptions of female song are rare. Here we report a detailed analysis of song in a small number of spontaneously-singing female domesticated canaries (Serinus canaria) under non-breeding, laboratory conditions in a large population of domesticated birds. In-depth analysis showed that these females sang rarely, and the spontaneous songs varied between and within birds over time. Furthermore, spontaneous female songs were distinct from songs of testosterone-induced singing female canaries and from songs of male canaries in both temporal and spectral features. Singing females had significantly elevated plasma androgen levels and a larger size of the major song controlling brain nuclei HVC (used as a proper name) and the robust nucleus of the arcopallium (RA) than non-singing females housed under similar conditions. The sporadically observed production of song and accompanying differences in brain anatomy in female canaries may thus depend on minute intraspecific differences in androgen levels.

Almost fifty years ago the advent of assay methods to measure circulating levels of hormones revolutionized endocrinology in relation to investigations of free-living and captive animals. This new field “environmental endocrinology” revealed that endocrine profiles in animals in their natural habitat were not only different from captive animals, but often deviated from predictions. It quickly became apparent that the organization and analysis of data from the field should be sorted by life history stages such as for reproductive processes, migration, molt etc. and spaced in time according to natural duration of those processes. Presentation of data by calendar date alone gives much simpler, even misleading, patterns. Stage-organized analyses revealed species-specific patterns of hormone secretion and dramatic inter-individual differences. The “Challenge Hypothesis” sparked exploration of these results, which diverged from expectations of hormone-behavior interactions. The hypothesis led to specific predictions about how the hypothalamo-pituitary-gonad axis, and particularly circulating patterns of testosterone, might respond to social challenges such as simulated territorial intrusions. Initially, a group of studies on free-living and captive birds played a key role in the formulation of the hypothesis. Over the decades since, the effects of social challenge and environmental context on hormonal responses have been tested in all vertebrate taxa, including humans, as well as in insects. Although it is now clear that the Challenge Hypothesis in its original form is simplistic, field and laboratory tests of the hypothesis have led to other concepts that have become seminal to the development of environmental endocrinology as a field. In this special issue these developments are addressed and examples from many different taxa enrich the emerging concepts, paving the way for investigations using recent technologies for genetic and transcriptome analyses.

Adolescence is a developmental period that is associated with physical, cognitive, and affective maturation and a time when sex biases in multiple psychiatric diseases emerge. While puberty onset marks the initiation of adolescence, it is unclear whether the pubertal rise in gonadal hormones generates sex differences in approach-avoidance behaviors that may impact psychiatric vulnerability. To examine the influence of pubertal development on adult behavior, we removed the gonads or performed sham surgery in male and female mice just prior to puberty onset and assessed performance in an odor-guided foraging task and anxiety-related behaviors in adulthood. We observed no significant sex differences in foraging or anxiety-related behaviors between intact adult male and female mice but found significant differences between adult male and female mice that had been gonadectomized (GDX) prior to puberty onset. GDX males failed to acquire the odor-guided foraging task, showed reduced locomotion, and exhibited increased anxiety-like behavior, while GDX females showed the opposite pattern of behavior. These data suggest that puberty may minimize rather than drive differences in approach-avoidance phenotypes in male and female mice.

Level of corticosterone (CORT), which is a predominant glucocorticoid in birds, has become the main indicator for assessing the stress level of birds in ecological studies. Feather corticosterone (CORTf) provides information about corticosterone levels during feather growth, however, the underlying causes of individual variation of CORTf between individuals and individual persistency of CORTf are not yet fully understood. Therefore, this study addresses individual consistency in CORTf and the association of variation in CORTf with behaviour that results in damage to tail feathers. We studied relations between CORTf, plasma CORT, and behaviour in wild-caught male greenfinches in captivity. CORTf in wild-grown feathers correlated positively with CORTf in lab-grown feathers. CORTf levels were about 20% lower in lab-grown feathers than in those grown in the wild. Four birds that died in captivity had significantly higher average CORTf levels in wild-grown feathers than the survivors. Plasma CORT levels of two measurements taken in the lab seven days apart correlated positively, however, no correlations between plasma CORT and CORTf were found. In order to study the link between CORTf and behaviour, the extent of tail damage from flapping against cage bar was assessed. Contrary to our prediction, birds with higher CORTf had less tail damage. This study adds to the evidence that CORTf levels can be considered as informative markers of some persistent component of individual phenotypic quality that can predict survival under standardized laboratory conditions.

Glucocorticoids are commonly associated with responses to stress, but other important functions include homeostatic regulation, energy metabolism and tissue remodeling. At low circulating levels, glucocorticoids bind to high-affinity mineralocorticoid receptors (MR) to activate tissue repair and homeostasis (anabolic pathways), whereas at elevated levels, glucocorticoids bind to glucocorticoid receptors (GR) to activate catabolic pathways. Long distance migrations, such as those performed by Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii), require modification of anatomy, physiology and behavior. Plasma corticosterone (CORT) increases in association with impending departure and flight and may promote muscle-specific anabolic states. To test this idea, we explored glucocorticoid signaling in the pectoralis (flight) and gastrocnemius (leg) muscles of male sparrows on the wintering grounds at three stages leading up to spring departure: winter (February), pre-nuptial molt (March), and pre-departure (April). CORT was detected in plasma and in both muscles, but measures of CORT signaling differed across muscles and stages. Expression of 11β-hydroxysteroid dehydrogenase (11β-HSD) Type 2 (inactivates CORT) increased in the pectoralis at pre-departure, whereas 11β-HSD Type 1 (regenerates CORT) did not change. Neither of the two 11β-HSD isoforms was detectable in the gastrocnemius. Expression of MR, but not GR, was elevated in the pectoralis at pre-departure, while only GR expression was elevated at pre-nuptial molt in gastrocnemius. These data suggest that anabolic functions predominate in the pectoralis only while catabolic activity is undetected in either muscle at pre-departure.

There is evidence that testosterone and cortisol levels are related to the attraction of a romantic partner; testosterone levels relate to a wide range of sexual behaviors and cortisol is a crucial component in the response to stress. To investigate this, we conducted a speed-dating study among heterosexual singles. We measured salivary testosterone and cortisol changes in men and women (n = 79) when they participated in a romantic condition (meeting opposite-sex others, i.e., potential romantic partners), as well as a control condition (meeting same-sex others, i.e., potential friends). Over the course of the romantic speed-dating event, results showed that women's but not men's testosterone levels increased and cortisol levels decreased for both men and women. These findings indicate that men's testosterone and cortisol levels were elevated in anticipation of the event, whereas for women, this appears to only be the case for cortisol. Concerning the relationship between attraction and hormonal change, four important findings can be distinguished. First, men were more popular when they arrived at the romantic speed-dating event with elevated cortisol levels. Second, in both men and women, a larger change in cortisol levels during romantic speed-dating was related to more selectivity. Third, testosterone alone was unrelated to any romantic speed-dating outcome (selectivity or popularity). However, fourth, women who arrived at the romantic speed-dating event with higher testosterone levels were more selective when their anticipatory cortisol response was low. Overall, our findings suggest that changes in the hormone cortisol may be stronger associated with the attraction of a romantic partner than testosterone.

Research on hormonal involvement in animals' preferences for mating or pairing with same- or other-sex partners has been among the topics featured in Hormones and Behavior over the years. In several species of non-pair-forming mammals, there is good evidence that the early sex steroid environment has an organizational effect on later sexual partner preference. Research with zebra finches, a pair-forming species, shows a likely early estrogenic organizational hormone effect on pairing partner preference, an effect that can also interact with the early social environment to determine adult pairing preference. Experiments with two amphibian and fish species suggest that activational hormone effects (effects of the hormone milieu in adulthood) may regulate sexual partner preference. As a complement to the research on hormonal involvement, a growing body of theoretical and empirical research addresses the possible adaptive functions of the same-sex sexual and pairing behavior observed in many wild animals. Such advances have important implications for conceptualizing neuroendocrine mechanisms of partner preferences.

Affiliative social relationships are impacted by stressors and can shape responses to stress. However, the effects of stress on social relationships in different contexts are not well understood. Meadow voles provide an opportunity to study these effects on peer relationships outside of a reproductive context. In winter months, female meadow voles cohabit with peers of both sexes, and social huddling is facilitated by exposure to short, winter-like day lengths in the lab. We investigated the role of stress and corticosterone (cort) levels in social behavior in short day-housed female meadow voles. A brief forced swim elevated cort levels, and we assessed the effects of this stressor on new and established relationships between females. In pairs formed following exposure to swim stress, the stressor significantly reduced the fraction of huddling time subjects spent with a familiar partner. Swim stress did not affect partner preferences in pairs established prior to the stressor. Finally, we examined fecal glucocorticoid metabolite levels via immunoassay in voles housed under short day (10h light) versus long day (14 h light) conditions and detected higher glucocorticoid levels in long day-housed voles. These findings support a role for stress regulation in the formation of social relationships in female meadow voles, and are consistent with a potential role for seasonal variation in cort in the behavioral transition from solitary to social. Together they highlight the importance of stress and possibly glucocorticoid signaling for social behavior.

The putative estrogen receptor GPER1 (the former orphan receptor GPR30) is discussed to be involved in emotional and cognitive functions and stress control. We recently described the induction of anxiety-like effects by the GPER1 agonist G-1 upon systemic injection into mice. To contribute to a better understanding of the role of GPER1 in anxiety and stress, we investigated germ-line GPER1 deficient mice. Our experiments revealed marked differences between the sexes. A mild but consistent phenotype of increased exploratory drive was observed in the home cage, the elevated plus maze and the light-dark choice test in male GPER1 KO mice. In contrast, female GPER1-KO mice displayed a less pronounced phenotype in these tests. Estrous-stage dependent mild anxiolytic-like effects were observed solely in the open field test. Notably, we observed a strong shift in acute stress coping behavior in the tail suspension test and basal corticosterone levels in different phases of the estrous cycle in female GPER1-KO mice. Our data, in line with previous reports, suggest that GPER1 is involved in anxiety and stress control. Surprisingly, its effects appear to be stronger in male than female mice.

Adult neuroplasticity in the song control system of seasonal songbirds is largely driven by photoperiod-induced increases in testosterone. Prior studies of the relationships between testosterone, song performance and neuroplasticity used invasive techniques, which prevent analyzing the dynamic changes over time and often focus on pre-defined regions-of-interest instead of examining the entire brain. Here, we combined (i) in vivo diffusion tensor imaging (DTI) to assess structural neuroplasticity with (ii) repeated monitoring of song and (iii) measures of plasma testosterone concentrations in thirteen female photosensitive starlings (Sturnus vulgaris) who received a testosterone implant for 3 weeks. We observed fast (days) and slower (weeks) effects of testosterone on song behavior and structural neuroplasticity and determined how these effects correlate on a within-subject level, which suggested separate contributions of the song motor and anterior forebrain pathways in the development of song performance. Specifically, the increase in testosterone correlated with a rapid increase of song rate and RA volume, and with changes in Area X microstructure. After implant removal, these variables rapidly reverted to baseline levels. In contrast, the more gradual improvement of song quality was positively correlated with the fractional anisotropy values (DTI metric sensitive to white matter changes) of the HVC-RA tract and of the lamina mesopallialis, which contains fibers connecting the song control nuclei. Thus, we confirmed many of the previously reported testosterone-induced effects, like the increase in song control nuclei volume, but identified for the first time a more global picture of the spatio-temporal changes in brain plasticity.

A key goal in behavioral ecology is to investigate the factors influencing the access to food resources and energetic condition of females, which are strong predictors of their reproductive success. We aimed to investigate how ecological factors, social factors, and reproductive state are associated with energetic condition in a wild neotropical primate using non-invasive measures. We first assessed and compared urinary C-peptide levels (uCP), the presence of urinary ketones (uKet), and behaviorally assessed energy balance (bEB) in female white-faced capuchin monkeys (Cebus imitator) living in Santa Rosa, Costa Rica. Then, we assessed how these measures were associated with feeding competition, dominance rank, and reproductive status. As predicted, uCP and bEB were positively associated with each other, and bEB was negatively associated with uKet. However, we did not find a relationship between uCP and uKet. Females showed lower uCP and bEB values during periods of intense feeding competition, but this relationship was not dependent on dominance rank. Furthermore, rank was not directly associated with uCP and bEB. Urinary ketones, on the other hand, were only produced in the most adverse conditions: by low-ranking, lactating females during periods of intense food competition. Behavioral strategies are assumed to maximize reproductive success and not energetic condition per se, which might explain why rank was not generally associated with energetic condition in our study population. This highlights the importance of considering potential differences between reproductive success and proxies of reproductive success, such as energetic condition or food intake, when investigating predictions of socioecological models.

Most mammal studies on the neuroendocrine mechanisms of territorial aggression have demonstrated that testosterone (T) is required for the display of territorial aggression. However, the relationship between T and aggression is more complex and may be modulated by social factor. The aim of this study was to determine the role of T in territorial aggression in the Mongolian gerbil (Meriones unguiculatus), and the effect of social factors on the modulation of this behavior. The relationship between T and territorial aggression was analyzed using castration and T replacement in two social contexts: male-male and male-female cohabitation. Plasma T concentrations in males of all groups were quantified by radioimmunoassay (RIA). T concentrations were compared using two-way ANOVA. Only sham-castrated and castrated males with T replacement in male-female cohabitation showed aggression, whereas castrated gerbils in the same condition were not aggressive. This indicates that T is the hormone that maintains territorial aggression, but mating is a modulator stimulus. The modulator effect of mating in territorial aggression was associated with an increase in T, but it seems that other mechanisms are involved in the regulation of this behavior, since castrated males with T replacement in the male-male cohabitation did not exhibit aggression, although they had T concentrations as high as these males that received the same treatment, but that cohabited with a female. These results suggest that T is involved in the mechanisms that regulate territorial aggression in the male Mongolian gerbil, and that the cohabitation with a female modulates this behavior.

Some seasonally-breeding animals are more aggressive during the short, "winter-like" days (SD) of the non-breeding season, despite gonadal regression and reduced circulating androgen levels. While the mechanisms underlying SD increases in aggression are not well understood, previous work from our lab suggests that pineal melatonin (MEL) and the adrenal androgen dehydroepiandrosterone (DHEA) are important in facilitating non-breeding aggression in Siberian hamsters (Phodopus sungorus). To characterize the role of MEL in modulating seasonal transitions in aggressive behavior, we housed male hamsters in long days (LD) or SD, treated them with timed MEL (M) or saline injections, and measured aggression after 3, 6, and 9 weeks. Furthermore, to assess whether MEL mediates seasonal shifts in gonadal and adrenal androgen synthesis, serum testosterone (T) and DHEA concentrations were quantified 36 h before and immediately following an aggressive encounter. LD-M and SD males exhibited similar physiological and behavioral responses to treatment. Specifically, both LD-M and SD males displayed higher levels of aggression than LD males and reduced circulating DHEA and T in response to an aggressive encounter, whereas LD males elevated circulating androgens. Interestingly, LD and SD males exhibited distinct relationships between circulating androgens and aggressive behavior, in which changes in serum T following an aggressive interaction (∆T) were negatively correlated with aggression in LD males, while ∆DHEA was positively correlated with aggression in SD males. Collectively, these findings suggest that SD males transition from synthesis to metabolism of circulating androgens following an aggressive encounter, a mechanism that is modulated by MEL.

The neuropeptides oxytocin and vasopressin have increasingly been identified as modulators of human social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction, such as autism. Identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition. Advances in human non-invasive neuroimaging techniques and genetics have enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. Here we review the findings to-date from investigations of the acute and chronic effects of oxytocin and vasopressin on neural activity underlying social cognitive processes using "pharmacological fMRI" and "imaging genetics", respectively. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.