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Sex and age affect depot expression of Ca2+ channels in rat white fat adipocytes J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-05-01 Yan Meng, Maria Toledo-Rodriguez, Olena Fedorenko, Paul A Smith
White adipose tissue (WAT) requires extracellular Ca2+ influx for lipolysis, differentiation, and expansion. This partly occurs via plasma membrane Ca2+ voltage-dependent channels (CaVs). However, WFA exists in different depots whose function varies with age, sex, and location. To explore whether their CaV expression profiles also differ we used RNAseq and qPCR on gonadal, mesenteric, retroperitoneal
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Cellular mechanisms of incretin hormone secretion J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-05-01 Marta Santos-Hernández, Frank Reimann, Fiona M Gribble
Enteroendocrine cells located along the gastrointestinal epithelium sense different nutrients/luminal contents that trigger the secretion of a variety of gut hormones with different roles in glucose homeostasis and appetite regulation. The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are involved in the regulation of insulin secretion, appetite
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Conserved and divergent features of trophoblast stem cells J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-05-01 Nirvay Sah, Francesca Soncin
Trophoblast stem cells (TSCs) are a proliferative multipotent population derived from the trophectoderm of the blastocyst, which will give rise to all the functional cell types of the trophoblast compartment of the placenta. The isolation and culture of TSCs in vitro represent a robust model to study mechanisms of trophoblast differentiation into mature cells both in successful and diseased pregnancy
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Follicle-stimulating hormone accelerates osteoclast migration by enhancing methyltransferase-like 3-mediated m6A methylation of cathepsin K J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-04-01 Xiaosa Li, Chao Fan, Jiale Wang, Ping Li, Xingyan Xu, Ruixin Guo, Jinzhi Wei, Yang Cheng, Huiping Lin, Xiaodong Fu
Follicle-stimulating hormone (FSH) accelerates osteoporosis in postmenopausal women, while the underlying mechanism remains uncharacterized. N6-methyladenosine (m6A) is one of the most important regulations in the development of osteoporosis. In this study, we aimed to investigate the role of FSH in m6A modification and osteoclast function. Here, we showed that FSH upregulated m6A levels in osteoclasts
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No extra-adrenal aldosterone production in various human cell lines J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-04-01 Isabelle Durrer, Daniel Ackermann, Rahel Klossner, Michael Grössl, Clarissa Vögel, Therina Du Toit, Bruno Vogt, Heidi Jamin, Markus G Mohaupt, Carine Gennari-Moser
Extra-adrenal de novo aldosterone (Aldo) production has been described inconsistently. Systematic data based upon state-of-the-art technology including validated controls are sparse. We hypothesized that aldosterone synthase (CYP11B2) expression and de novo Aldo production are absent in nonadrenal human cell lines, either immortalized cell lines or commercially available primary cell lines, including
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Mutant Tbl1x male mice have a short lifespan and do not breed: unexpected findings J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-02-01 Yalan Hu, Gemma F Codner, Michelle Stewart, Susanne E La Fleur, Paul As van Trotsenburg, Eric Fliers, Raoul C Hennekam, Anita Boelen
Humans with the mutation Y509C in transducin beta like 1 X-linked (TBL1X HGNC ID HGNC:11585) have been reported to present with the combination of central congenital hypothyroidism and impaired hearing. TBL1X belongs to the WD40 repeat-containing protein family, is part of NCoR and SMRT corepressor complexes, and thereby involved in thyroid hormone signaling. In order to investigate the effects of
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AMPK–mTORC1 pathway mediates hepatic IGFBP-1 phosphorylation in glucose deprivation: a potential molecular mechanism of hypoglycemia-induced impaired fetal growth J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-04-01 Jenica H Kakadia, Muhammad U Khalid, Ilka U Heinemann, Victor K Han
Mechanisms underlying limitations in glucose supply that restrict fetal growth are not well established. IGF-1 is an important regulator of fetal growth and IGF-1 bioavailability is markedly inhibited by IGFBP-1 especially when the binding protein is hyperphosphorylated. We hypothesized that the AMPK–mTORC1 pathway increases IGFBP-1 phosphorylation in response to glucose deprivation. Glucose deprivation
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New methods to investigate the GnRH pulse generator J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-02-01 Deyana Ivanova, Kevin T O’Byrne
The exact neural construct underlying the dynamic secretion of gonadotrophin-releasing hormone (GnRH) has only recently been identified despite the detection of multiunit electrical activity volleys associated with pulsatile luteinising hormone (LH) secretion four decades ago. Since the discovery of kisspeptin/neurokinin B/dynorphin neurons in the mammalian hypothalamus, there has been much research
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Oxidative and ER stress by elevated insulin biosynthesis and palmitic acid in insulin-producing cells J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-02-01 Brenda Vidrio-Huerta, Thomas Plötz, Stephan Lortz
The early phase of type 2 diabetes mellitus (T2DM) is characterised by insulin resistance, which can initially be compensated by elevated insulin secretion. However, as postulated by the workload hypothesis, over time harming insulin requirements contribute to β-cell dysfunction and death. The mechanisms behind this transition are complex and not fully understood but involve factors such as endoplasmic
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N1-methylnicotinamide impairs gestational glucose tolerance in mice J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-02-01 Xiaojing Wei, Yutian Tan, Jiaqi Huang, Ximing Dong, Weijie Feng, Tanglin Liu, Zhao Yang, Guiying Yang, Xiao Luo
N1-methylnicotinamide (MNAM), a product of methylation of nicotinamide through nicotinamide N-methyltransferase, displays antidiabetic effects in male rodents. This study aimed to evaluate the ameliorative potential of MNAM on glucose metabolism in a gestational diabetes mellitus (GDM) model. C57BL/6N mice were fed with a high-fat diet (HFD) for 6 weeks before pregnancy and throughout gestation to
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Development and characterisation of a novel inhibitory anti-GH monoclonal antibody J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-01-01 Man Lu, Chantal Buckley, Yue Wang, Ries J Langley, Jo K Perry
Excess growth hormone (GH) has been implicated in multiple cancer types and there is increasing interest in the development of therapeutic inhibitors targeting GH–GH receptor (GHR) signalling. Here we describe a panel of anti-GH monoclonal antibodies (mAbs) generated using a hybridoma approach and identify two novel inhibitory mAbs (1-8-2 and 1-46-3) that neutralised GH signalling. mAbs 1-8-2 and 1-46-3
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Pseudohypoparathyroidism: complex disease variants with unfortunate names J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-01-01 Harald Jüppner
Several human disorders are caused by genetic or epigenetic changes involving the GNAS locus on chromosome 20q13.3 that encodes the alpha-subunit of the stimulatory G protein (Gsα) and several splice variants thereof. Thus, pseudohypoparathyroidism type Ia (PHP1A) is caused by heterozygous inactivating mutations involving the maternal GNAS exons 1–13 resulting in characteristic abnormalities referred
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Retinoic acid regulation of homoeostatic synaptic plasticity and its relationship to cognitive disorders J. Mol. Endocrinol. (IF 3.5) Pub Date : 2024-01-01 Francesca Moramarco, Peter McCaffery
There is increasing interest in retinoic acid (RA) as a regulator of the complex biological processes underlying the cognitive functions performed by the brain. The importance of RA in brain function is underlined by the brain’s high efficiency in converting vitamin A into RA. One crucial action of RA in the brain is dependent on RA receptor α (RARα) transport out of the nucleus, where it no longer
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G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-11-01 Emily M Hawes, Kayla A Boortz, James K Oeser, Margaret L O’Rourke, Richard M O’Brien
In the endoplasmic reticulum (ER) lumen, glucose-6-phosphatase catalytic subunit 1 and 2 (G6PC1; G6PC2) hydrolyze glucose-6-phosphate (G6P) to glucose and inorganic phosphate whereas hexose-6-phosphate dehydrogenase (H6PD) hydrolyzes G6P to 6-phosphogluconate (6PG) in a reaction that generates NADPH. 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) utilizes this NADPH to convert inactive cortisone
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Impact of placental mTOR deficiency on peripheral insulin signaling in adult mice offspring J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-11-01 Megan Beetch, Brian Akhaphong, Alicia Wong, Briana Clifton, Seokwon Jo, Ramkumar Mohan, Juan E Abrahante Llorens, Emilyn U Alejandro
Suboptimal in utero environments such as poor maternal nutrition and gestational diabetes can impact fetal birth weight and the metabolic health trajectory of the adult offspring. Fetal growth is associated with alterations in placental mechanistic target of rapamycin (mTOR) signaling; it is reduced in fetal growth restriction and increased in fetal overgrowth. We previously reported that when metabolically
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Characterisation of the hydrogen sulfide system in early diabetic kidney disease J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-11-01 Caroline J Bushell, Leonard G Forgan, Kathryn Aston-Mourney, Timothy Connor, Sean L McGee, Bryony A McNeill
A deficiency in hydrogen sulfide has been implicated in the development and progression of diabetic chronic kidney disease. The purpose of this study was to determine the effect of diabetes on the H2S system in early-stage diabetic kidney disease. We characterised gene and protein expression profile of the enzymes that regulate H2S production and degradation, and H2S production capacity, in the kidney
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RISING STARS: Role of MED12 mutation in the pathogenesis of uterine fibroids J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-11-01 Hiroshi Ishikawa, Tatsuya Kobayashi, Meika Kaneko, Yoshiko Saito, Makio Shozu, Kaori Koga
Graphical abstract Abstract Uterine fibroids (UFs) are benign tumors arising from the uterus, characterized by accumulation of abundant extracellular matrix (ECM) and sex steroid-dependent growth. Women with symptomatic UFs have reduced quality of life and decreased labor productivity. Among the driver gene mutations identified in UFs, mutations in MED12, a component of the cyclin-dependent kinase
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Vascular endothelial mineralocorticoid receptors and epithelial sodium channels in metabolic syndrome and related cardiovascular disease J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-10-01 Guanghong Jia, Michael A Hill, James R Sowers
Metabolic syndrome is a group of risk factors that increase the risk of developing metabolic and cardiovascular disease (CVD) and include obesity, dyslipidemia, insulin resistance, atherosclerosis, hypertension, coronary artery disease, and heart failure. Recent research indicates that excessive production of aldosterone and associated activation of mineralocorticoid receptors (MR) impair insulin metabolic
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Erythropoietin-mediated cardioprotection in hearts subjected to ischemia reperfusion J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-10-01 Débora Elisabet Vélez, Victoria Evangelina Mestre Cordero, Romina Hermann, María de las Mercedes Fernández Pazos, Federico Joaquín Reznik, Lucia Sánchez, María Gabriela Marina Prendes
Several studies provide evidence that erythropoietin (EPO) could play an important role in the recovery of the heart subjected to ischemia–reperfusion. In this regard, it has been suggested that EPO could be involved in protein kinase B (Akt) activation as a cell survival protein. The aim of the present study was to investigate the effects of EPO on the Akt/glycogen synthase kinase 3 beta (GSK-3β)
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Inhibition of mitochondrial fission and protein kinase R improves progesterone in placental stress J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-10-01 Umut Kerem Kolac
Placenta synthesizes hormones that play a vital role in adapting maternal physiology and supporting fetal growth. This study aimed to explore the link between progesterone, a key steroid hormone produced by placenta, and mitochondrial fission and protein kinase R through the use of chemical inhibition in trophoblasts subjected to endotoxin lipopolysaccharide and double-stranded RNA analog polyinosinic:polycytidylic
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Maternal obesity attenuates PPARγ nuclear migration impairing offspring adipogenesis J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-10-01 Érica de Sousa, Alice Cristina Rodrigues
Maternal obesity predisposes offspring to obesity in adulthood. Since the perinatal period is a critical window for adipose organogenesis, we evaluated if maternal obesity affects the perinatal offspring adipogenesis. Female mice were fed a standard diet (eutrophic dam, ED) or a high-fat diet supplemented with condensed milk (obese dam, OD) for 6 weeks before mating, and the diets were maintained until
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Evaluation of hippocampal arylalkylamine N-acetyltransferase activity in amyloid-β neurotoxicity J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-08-01 Shima Mohammadi, Maryam Zahmatkesh, Yazdan Asgari, Samaneh Aminyavari, Gholamreza Hassanzadeh
Arylalkylamine N-acetyltransferase (AANAT), a rate-limiting enzyme in melatonin synthesis, is present in extra-pineal tissues such as the hippocampus. The hippocampal AANAT activity in amyloid β (Aβ) neurotoxicity has not been exactly defined. Adult male rats received bilateral intra-CA1 Aβ administration. The hippocampus tissue sampling was performed 2, 12, and 24 h after Aβ injection in the morning
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Role of serum- and glucocorticoid-inducible kinase 1 in the regulation of hepatic gluconeogenesis J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-08-01 Zhaoqian Xu, Yiru Wang, Qianqian Liu, Shushu Wang, Chunxiang Sheng, Junmin Chen, Jialin Tan, Xiao Wang, Li Shao, Libin Zhou
Excessive hepatic gluconeogenesis partially accounts for the occurrence of type 2 diabetes mellitus. Serum- and glucocorticoid inducible-kinase 1 (SGK1) is linked to the development of metabolic syndrome, such as obesity, hypertension, and hyperglycemia. However, the regulatory role of SGK1 in glucose metabolism of liver remains uncertain. Our microarray analysis showed that SGK1 expression was strongly
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In silico study to unravel molecular networking of melatonin in the regulation of gametogenesis J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-08-01 Akash Acharyya, Joydeep Das, Kazi Nurul Hasan
Melatonin, a pineal hormone, has potential role on steroidogenesis, growth and maturation of sperm and ovum during gametogenesis. The possible use of this indolamine as an antioxidant in the production of good quality gametes opens up a new area of current research. Nowadays, a large number of reproductive dysfunctions like infertility and failure in fertilization due to gametic malformations are major
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RISING STARS: Liver sinusoidal endothelial transcription factors in metabolic homeostasis and disease J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-08-01 Dorka Nagy, Hannah Maude, Graeme M Birdsey, Anna M Randi, Inês Cebola
Liver sinusoidal endothelial cells (LSECs) are highly specialised endothelial cells that form the liver microvasculature. LSECs maintain liver homeostasis, scavenging bloodborne molecules, regulating immune response, and actively promoting hepatic stellate cell quiescence. These diverse functions are underpinned by a suite of unique phenotypical attributes distinct from other blood vessels. In recent
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Neuropeptide Y regulates osteocyte phenotype and function through AHNAK-Smad signalling J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-08-01 Xiangnan Wu, Yiqiao Wang, Hang Wang, Meirui Ma, Zhichao Hao, Yuanyuan Ma
Neuropeptide Y (NPY) is a widespread hormone in the central and peripheral nervous systems that maintains body homeostasis. Central actions of hypothalamic NPY have been identified in bone metabolism. Osteocytes are the main source of NPY in bone tissue, indicating that osteocytic NPY could be a local alternative pathway for hypothalamic mediated regulation of bone and bone cells. Here, we show that
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Sex steroids have opposing effects on heart rate of juveniles, Gambusia holbrooki J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-08-01 Seyed Ehsan Mousavi, Komeil Razmi, Jawahar G Patil
Graphical abstract Abstract Built on our recent work that heart rates (HRs) and function in Gambusia holbrooki are sexually dimorphic, this study assessed whether the species is an appropriate model to study sex-hormone effects on heart physiology. With a hypothesis that 17β-estradiol (E2) and 17α-methyltestosterone (MT) regulate the HR of juvenile G. holbrooki in a sex-specific manner, genetic males
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CLEC11A improves insulin secretion and promotes cell proliferation in human beta-cells J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-07-01 Ruifeng Shi, Jing Cen, Gunilla T Westermark, Sheng Zhao, Nils Welsh, Zilin Sun, Joey Lau
Beta-cell dysfunction is a hallmark of disease progression in patients with diabetes. Research has been focused on maintaining and restoring beta-cell function during diabetes development. The aims of this study were to explore the expression of C-type lectin domain containing 11A (CLEC11A), a secreted sulphated glycoprotein, in human islets and to evaluate the effects of CLEC11A on beta-cell function
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The role of WD40 repeat-containing proteins in endocrine (dys)function J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-07-01 Yalan Hu, Eveline Bruinstroop, Anthony N Hollenberg, Eric Fliers, Anita Boelen
WD40 repeat-containing proteins play a key role in many cellular functions including signal transduction, protein degradation, and apoptosis. The WD40 domain is highly conserved, and its typical structure is a β-propeller consisting of 4–8 blades which probably serves as a scaffold for protein–protein interaction. Some WD40 repeat-containing proteins form part of the corepressor complex of nuclear
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A unique melanocortin-4-receptor signaling profile for obesity-associated constitutively active variants J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-07-01 Rikus Botha, Shree S Kumar, Natasha L Grimsey, Kathleen G Mountjoy
The melanocortin-4 receptor (MC4R) plays a critical role in regulating energy homeostasis. Studies on obesogenic human MC4R (hMC4R) variants have not yet revealed how hMC4R maintains body weight. Here, we identified a signaling profile for obesogenic constitutively active H76R and L250Q hMC4R variants transfected in HEK293 cells that included constitutive activity for adenylyl cyclase (AC), cyclic
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A time- and space-resolved nuclear receptor atlas in mouse liver J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-07-01 Francesco Paolo Zummo, Alexandre Berthier, Céline Gheeraert, Manjula Vinod, Marie Bobowski-Gérard, Olivier Molendi-Coste, Laurent Pineau, Matthieu Jung, Loic Guille, Julie Dubois-Chevalier, David Dombrowicz, Bart Staels, Jérôme Eeckhoute, Philippe Lefebvre
The functional versatility of the liver is paramount for organismal homeostasis. Adult liver functions are controlled by a tightly regulated transcription factor network including nuclear receptors (NRs), which orchestrate many aspects of hepatic physiology. NRs are transcription factors sensitive to extracellular cues such as hormones, lipids, xenobiotics, etc. and are modulated by intracellular signaling
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Transthyretin knockdown recapitulates the insulin-sensitizing effects of exercise and promotes skeletal muscle adaptation to exercise endurance J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-07-01 Beibei Wu, Ruojun Qiu, Shuo Wang, Yingzi He, Jing Wang, Zhiye Xu, Xihua Lin, Hong Li, Fenping Zheng
Liver transthyretin (TTR) synthesis and release are exacerbated in insulin-resistant states but are decreased by exercise training, in relation to the insulin-sensitizing effects of exercise. We hypothesized that TTR knockdown (TTR-KD) may mimic this exercise-induced metabolic improvement and skeletal muscle remodeling. Adeno-associated virus-mediated TTR-KD and control mice were trained for 8 weeks
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CEBPB/POU2F2 modulates endothelin 1 expression in prehypertensive SHR vascular smooth muscle cells J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-07-01 Tien-Chun Yang, Mei-Hua Lu, Wei-Jie Wang, Jang-Yi Chen
The pathogenesis of hypertension is not fully understood; endothelin 1 (EDN1) is involved in developing essential hypertension. EDN1 can promote vascular smooth muscle cell (VSMC) proliferation or hypertrophy through autocrine and paracrine effects. Proliferating smooth muscle cells in the aorta are 'dedifferentiated' cells that cause increased arterial stiffness and remodeling. Male SHRs had higher
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RISING STARS: Targeting G protein-coupled receptors to regulate energy homeostasis J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-05-01 Aqfan Jamaluddin, Caroline M Gorvin
G protein-coupled receptors (GPCRs) have a critical role in energy homeostasis, contributing to food intake, energy expenditure and glycaemic control. Dysregulation of energy expenditure can lead to metabolic syndrome (abdominal obesity, elevated plasma triglyceride, LDL cholesterol and glucose, and high blood pressure), which is associated with an increased risk of developing obesity, diabetes mellitus
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BMAL1 regulates osteoblast differentiation through mTOR/GSK3β/β-catenin pathway J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-05-01 Huixia Li, Hui Meng, Min Xu, Xin Gao, Xulei Sun, Xinxin Jin, Hongzhi Sun
Bone mass declines with age and its maintenance is tightly linked to osteoblasts (crucial bone-building cells). Although disruption of the peripheral circadian clock is involved in various pathologies including aging-related diseases, evidence regarding how the peripheral clock regulates bone mass remains elusive. In the present study, we aimed to elucidate the effects of Bmal1 (the key activator of
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PPP2R2A promotes testosterone secretion in Hu sheep Leydig cells via activation of the AKT/mTOR signaling pathway J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-05-01 Xiaodan Li, Xiaolei Yao, Yongjin Bao, Kaiping Deng, Mingtian Deng, Fan Yang, Xuan Sun, Peihua You, Qingxian Cai, Feng Wang
The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme complex that plays a vital role in regulating male reproductive activities. However, as an essential member of the PP2A family, the physiological functions of PP2A regulatory subunit B55α (PPP2R2A) in testis remain inconclusive. Hu sheep are noted for their reproductive precocity and fertility, and are ideal models for the
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βHB inhibits glucose-induced GLP-1 secretion in GLUTag and human jejunal enteroids J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-05-01 Erik Elebring, Anna Casselbrant, Sara M T Persson, Lars Fändriks, Ville Wallenius
Ingestion of nutrients stimulates incretin secretion from enteroendocrine cells (EECs) of the epithelial layer of the gut. Glucagon-like peptide-1 (GLP-1) is one of these incretins that stimulate postprandial insulin release and signal satiety to the brain. Understanding the regulation of incretin secretion might open up new therapeutic options for obesity and type-2 diabetes mellitus. To investigate
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CTCF variant begets to short stature by down-regulation of IGF1 J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-05-01 Hong Chen, Weiyu Li, Suping Zhang, Yunteng Sun, Yiping Shen, Ruimin Chen
Pathogenic variants in the transcription factor CCCTC-binding factor (CTCF) are associated with mental retardation, autosomal dominant 21 (MRD21, MIM#615502). Current studies supported the strong relationship between CTCF variants and growth, yet the mechanism of CTCF mutation leading to short stature is not known. Clinical information, treatment regimens, and follow-up outcomes of a patient with MRD21
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Phospholipase D mediates very low-density lipoprotein-induced aldosterone production, in part, via lipin-1 J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-05-01 Shinjini C Spaulding, Vivek Choudhary, Wendy B Bollag
Aldosterone is considered to be a link between hypertension and obesity; obese individuals have high serum levels of very low-density lipoprotein (VLDL). VLDL has been shown to induce aldosterone production in multiple adrenal zona glomerulosa models, mediated in part by phospholipase D (PLD). PLD is an enzyme that hydrolyzes phosphatidylcholine to produce phosphatidic acid (PA), a lipid second messenger
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Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-04-01 Rishel B Vohnoutka, Annapurna Kuppa, Yash Hegde, Yue Chen, Asmita Pant, Maurice E Tohme, Eun-Young (Karen) Choi, Sean M McCarty, Devika P Bagchi, Xiaomeng Du, Yanhua Chen, Vincent L Chen, Hiroyuki Mori, Lawrence F Bielak, Lillias H Maguire, Samuel K Handelman, Jonathan Z Sexton, Thomas L Saunders, Brian D Halligan, Elizabeth K Speliotes
Human genome-wide association studies found single-nucleotide polymorphisms (SNPs) near LYPLAL1 (Lysophospholipase-like protein 1) that have sex-specific effects on fat distribution and metabolic traits. To determine whether altering LYPLAL1 affects obesity and metabolic disease, we created and characterized a mouse knockout (KO) of Lyplal1. We fed the experimental group of mice a high-fat, high-sucrose
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Cotadutide effect in liver and adipose tissue in obese mice J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-04-01 Ilitch Aquino Marcondes-de-Castro, Thamiris Ferreira Oliveira, Renata Spezani, Thatiany Souza Marinho, Luiz Eduardo Macedo Cardoso, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Obesity, adipose tissue inflammation, and nonalcoholic fatty liver disease (NAFLD) are associated with insulin resistance and type 2 diabetes (T2D). Cotadutide is a dual agonist GLP-1/glucagon, currently in a preclinical study phase 2 that presents an anti-obesity effect. Diet-induced obese (DIO) C57BL/6 mice were treated for 4 weeks with cotadutide (30 nm/kg once a day at 14:00 h). The study focused
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Dysregulation of endoplasmic reticulum stress response in skin wounds in a streptozotocin-induced diabetes mouse model J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-04-01 Ermelindo C Leal, Tatiana Emanuelli, Diana Santos, João Moura, Ana Catarina RG Fonseca, Ana Burgeiro, Eugenia Carvalho
Dysfunction in key cellular organelles has been linked to diabetic complications. This study intended to investigate the alterations in the unfolded protein response (UPR), autophagy, and mitochondrial function, which are part of the endoplasmic reticulum (ER) stress response, in wound healing (WH) under diabetes conditions. WH mouse models were used to evaluate the UPR, autophagy, mitochondrial fusion
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RISING STARS: Hormonal regulation of the breast cancer microenvironment J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-04-01 Sarah Theresa Boyle
The tumor microenvironment is a dynamic ecosystem of stromal and immune cells that, under the influence of cancer cells, govern biochemical signaling, mechanical signaling via production and remodeling of the extracellular matrix (ECM), formation of vascular networks, and ultimately promotion of tumor growth. In breast cancer, hormone receptor-mediated signaling is a key coordinator of cancer cell
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Identification of prolactin receptor variants with diverse effects on receptor signalling J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-04-01 Caroline M Gorvin, Paul J Newey, Rajesh V Thakker
The prolactin receptor (PRLR) signals predominantly through the JAK2-STAT5 pathway regulating multiple physiological functions relating to fertility, lactation, and metabolism. However, the molecular pathology and role of PRLR mutations and signalling are incompletely defined, with progress hampered by a lack of reported disease-associated PRLR variants. To date, two common germline PRLR variants are
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Genetic bases of pheochromocytoma and paraganglioma J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-04-01 Alberto Cascón, Bruna Calsina, María Monteagudo, Sara Mellid, Alberto Díaz-Talavera, Maria Currás-Freixes, Mercedes Robledo
The genetics of pheochromocytoma and paraganglioma (PPGL) has become increasingly complex over the last two decades. The list of genes involved in the development of these tumors has grown steadily, and there are currently more than 20 driver genes implicated in either the hereditary or the sporadic nature of the disease. Although genetic diagnosis is achieved in about 75–80% of patients, genetic etiology
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Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-04-01 Stuart Baker, Ricardo Núñez Miguel, Daniel Thomas, Michael Powell, Jadwiga Furmaniak, Bernard Rees Smith
Determination of the structure of the extracellular domain of human thyroid peroxidase (hTPO) by cryo-electron microscopy (cryo-EM) is described. TPO, purified to homogeneity was complexed with the hTPO monoclonal autoantibody 2G4 Fab and also with a mouse monoclonal TPO antibody 4F5 Fab (which competes with autoantibody binding to TPO). Both complexes were analysed by cryo-EM. The two structures (global
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ERα/ERβ-directed CBS transcription mediates E2β-stimulated hUAEC H2S production J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-02-01 Jin Bai, Thomas J Lechuga, Joshua Makhoul, Hao Yan, Carol Major, Afshan Hameed, Dong-bao Chen
Elevated endogenous estrogens stimulate human uterine artery endothelial cell (hUAEC) hydrogen sulfide (H2S) production by selectively upregulating the expression of H2S synthesizing enzyme cystathionine β-synthase (CBS), but the underlying mechanisms are underdetermined. We hypothesized that CBS transcription mediates estrogen-stimulated pregnancy-dependent hUAEC H2S production. Estradiol-17β (E2β)
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Finnish-specific AKT2 gene variant leads to impaired insulin signalling in myotubes J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-02-01 Selina Mäkinen, Neeta Datta, Savithri Rangarajan, Yen H Nguyen, Vesa M Olkkonen, Aino Latva-Rasku, Pirjo Nuutila, Markku Laakso, Heikki A Koistinen
Finnish-specific gene variant p.P50T/AKT2 (minor allele frequency (MAF) = 1.1%) is associated with insulin resistance and increased predisposition to type 2 diabetes. Here, we have investigated in vitro the impact of the gene variant on glucose metabolism and intracellular signalling in human primary skeletal muscle cells, which were established from 14 male p.P50T/AKT2 variant carriers and 14 controls
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m6A readers, writers, erasers, and the m6A epitranscriptome in breast cancer J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-02-01 Belinda J Petri, Carolyn M Klinge
Epitranscriptomic modification of RNA regulates human development, health, and disease. The true diversity of the transcriptome in breast cancer including chemical modification of transcribed RNA (epitranscriptomics) is not well understood due to limitations of technology and bioinformatic analysis. N-6-methyladenosine (m6A) is the most abundant epitranscriptomic modification of mRNA and regulates
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GP73 blockade alleviates abnormal glucose homeostasis in diabetic mice J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-02-01 Xiaopan Yang, Xiaojing Fan, Jiangyue Feng, Tinghui Fan, Jingfei Li, Linfei Huang, Luming Wan, Huan Yang, Huilong Li, Jing Gong, Yanhong Zhang, Qi Gao, Fei Zheng, Lei Xu, Haotian Lin, Dandan Zhang, Hongbin Song, Yufei Wang, Xueping Ma, Zhiwei Sun, Cheng Cao, Xiaoli Yang, Hui Zhong, Yi Fang, Congwen Wei
Golgi protein 73 (GP73), also called Golgi membrane protein 1 (GOLM1), is a resident Golgi type II transmembrane protein and is considered as a serum marker for the detection of a variety of cancers. A recent work revealed the role of the secreted GP73 in stimulating liver glucose production and systemic glucose homeostasis. Since exaggerated hepatic glucose production plays a key role in the pathogenesis
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Effect of calcitriol and calcium on basal ganglia calcification in hypoparathyroidism: experimental models J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-02-01 Parmita Kar, Ravinder Goswami
Basal ganglia calcification (BGC) is a common complication in hypoparathyroid patients, linked to hyperphosphatemia and altered vitamin-D and calcium homeostasis following conventional therapy. The pathogenesis of BGC in hypoparathyroidism is not clear. Recently, we developed an ex vivo model of BGC using rat-striatal cell culture in 10.0 mmol/L of β-glycerophosphate (31.8 mg/dL phosphate). However
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Adipocyte signaling affects thyroid-specific gene expression via down-regulation of TTF-2/FOXE1 J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-01-01 Michela Zamboni, Georgios Strimpakos, Eleonora Poggiogalle, Lorenzo M Donini, Donato Civitareale
Obesity affects thyroid gland function. Hypothyroidism, thyroid nodules, goiter, and thyroid cancer are more frequent in patients with higher BMI values. Although these data are supported by many clinical and epidemiological studies, our knowledge is very scarce at the molecular level. In this study, we present the first experimental evidence that adipocyte signaling downregulates the expression of
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Melatonin alleviates diet-induced steatohepatitis by targeting multiple cell types in the liver to suppress inflammation and fibrosis J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-01-01 Liang Xu, Haoran Li, Ouyang Zhang, Fengming Zhang, Menghui Song, Mengchen Ma, Youjuan Zhao, Rongxiu Ding, Dandan Li, Zhixiong Dong, Shengnan Jin, Weiping Han, Chunming Ding
The pathogenesis of nonalcoholic steatohepatitis (NASH), a severe stage of nonalcoholic fatty liver disease, is complex and implicates multiple cell interactions. However, therapies for NASH that target multiple cell interactions are still lacking. Melatonin (MEL) alleviates NASH with mechanisms not yet fully understood. Thus, we herein investigate the effects of MEL on key cell types involved in NASH
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Embarking on an adventure of early career academic leadership J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-01-01 Tijana Mitić
Leading a research group as an early career researcher (ECR) in academia presents many challenges. First, it imposes many additional pressures on individuals, causing fear of missing out on a great opportunity that could advance your career. Together, the unsettling nature of short-term or temporary contracts, lack of guidance and the imposter syndrome can trigger a crisis in future leadership. Most
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The epidermal growth factor receptor in healthy pregnancy and preeclampsia J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-01-01 Luca Clemente, Ian M Bird
The epidermal growth factor receptor (EGFR) is expressed robustly in the placenta, and critical processes of pregnancy such as placental growth and trophoblast fusion are dependent on EGFR function. However, the role that aberrant EGFR signaling might play in the etiology and/or maintenance of preeclampsia (PE) remains largely unexplored. Recently, we have shown that overexpression of EGFR in cultured
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Structure of full-length TSH receptor in complex with antibody K1-70™ J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-01-01 Ricardo Núñez Miguel, Paul Sanders, Lloyd Allen, Michele Evans, Matthew Holly, William Johnson, Andrew Sullivan, Jane Sanders, Jadwiga Furmaniak, Bernard Rees Smith
Determination of the full-length thyroid-stimulating hormone receptor (TSHR) structure by cryo-electron microscopy (cryo-EM) is described. The TSHR complexed with human monoclonal TSHR autoantibody K1-70™ (a powerful inhibitor of TSH action) was detergent solubilised, purified to homogeneity and analysed by cryo-EM. The structure (global resolution 3.3 Å) is a monomer with all three domains visible:
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Regulation of mineralocorticoid receptor activation by circadian protein TIMELESS J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-01-01 Colin D Clyne, Kevin P Kusnadi, Alexander Cowcher, James Morgan, Jun Yang, Peter J Fuller, Morag J Young
The mineralocorticoid receptor (MR) is a ligand-activated transcription factor that regulates cardiorenal physiology and disease. Ligand-dependent MR transactivation involves a conformational change in the MR and recruitment of coregulatory proteins to form a unique DNA-binding complex at the hormone response element in target gene promoters. Differences in the recruitment of coregulatory proteins
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mPRα and PR co-operate in progesterone inhibition of endothelial cell focal adhesion J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-01-01 Yefei Pang, Peter Thomas
Progesterone causes vascular smooth muscle cell relaxation through membrane progesterone receptors (mPRs), which are members of the progestin and adipoQ receptor (PAQR) family, and nuclear PRs (nPRs). However, beneficial vascular effects of progesterone in preventing pre-atherosclerosis and the involvement of mPRs and nPRs remain unclear. The results show short- to long-term treatments with 100 nM
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Ataxin-2 in the hypothalamus at the crossroads between metabolism and clock genes J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-01-01 Sara Carmo-Silva, Marisa Ferreira-Marques, Clévio Nóbrega, Mariana Botelho, Daniela Costa, Célia A Aveleira, Stefan M Pulst, Luís Pereira de Almeida, Claudia Cavadas
ATXN2 gene, encoding for ataxin-2, is located in a trait locus for obesity. Atxn2 knockout (KO) mice are obese and insulin resistant; however, the cause for this phenotype is still unknown. Moreover, several findings suggest ataxin-2 as a metabolic regulator, but the role of this protein in the hypothalamus was never studied before. The aim of this work was to understand if ataxin-2 modulation in the
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Son of sevenless 1 (SOS1), the RasGEF, interacts with ERα and STAT3 during embryo implantation J. Mol. Endocrinol. (IF 3.5) Pub Date : 2023-01-01 Renjini A Padmanabhan, Damodaranpillai P Zyju, Anand G Subramaniam, Jaya Nautiyal, Malini Laloraya
Estrogen accounts for several biological processes in the body; embryo implantation and pregnancy being one of the vital events. This manuscript aims to unearth the nuclear role of Son of sevenless1 (SOS1), its interaction with estrogen receptor alpha (ERα), and signal transducer and activator of transcription 3 (STAT3) in the uterine nucleus during embryo implantation. SOS1, a critical cytoplasmic