Estradiol and testosterone are powerful steroid hormones that impact brain function in numerous ways. During development, these hormones can act to program the adult brain in a male or female direction. During adulthood, gonadal steroid hormones can activate or inhibit brain regions to modulate adult functions. Sex differences in behavioral and neuroendocrine (i.e., hypothalamic pituitary adrenal (HPA) axis) responses to stress arise as a result of these organizational and activational actions. The sex differences that are present in the HPA and behavioral responses to stress are particularly important considering their role in maintaining homeostasis. Furthermore, dysregulation of these systems can underlie the sex biases in risk for complex, stress-related diseases that are found in humans. Although many studies have explored the role of estrogen and estrogen receptors in mediating sex differences in stress-related behaviors and HPA function, much less consideration has been given to the role of androgens. While circulating androgens can act by binding and activating androgen receptors, they can also act by metabolism to estrogenic molecules to impact estrogen signaling in the brain and periphery. This review focuses on androgens as an important hormone for modulating the HPA axis and behaviors throughout life and for setting up sex differences in key stress regulatory systems that could impact risk for disease in adulthood. In particular, impacts of androgens on neuropeptide systems known to play key roles in HPA and behavioral responses to stress (corticotropin-releasing factor, vasopressin, and oxytocin) are discussed. A greater knowledge of androgen action in the brain is key to understanding the neurobiology of stress in both sexes.

中文翻译：

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雄激素在调节神经内分泌和行为应激反应的性别差异中的作用。

雌二醇和睾酮是强大的类固醇激素，可以通过多种方式影响大脑功能。在发育过程中，这些激素可以在男性或女性的方向上对成人大脑进行编程。在成年期，性腺类固醇激素可以激活或抑制大脑区域来调节成人功能。行为和神经内分泌（即下丘脑垂体肾上腺 (HPA) 轴）对压力反应的性别差异是这些组织和激活行动的结果。考虑到它们在维持体内平衡中的作用，HPA 中存在的性别差异和对压力的行为反应尤为重要。此外，这些系统的失调可能是人类发现的复杂的、与压力相关的疾病风险的性别偏见的基础。尽管许多研究探索了雌激素和雌激素受体在介导压力相关行为和 HPA 功能方面的性别差异中的作用，但很少考虑雄激素的作用。虽然循环雄激素可以通过结合和激活雄激素受体发挥作用，但它们也可以通过代谢雌激素分子来影响大脑和外周的雌激素信号。本综述的重点是雄激素作为一种重要的激素，用于在整个生命过程中调节 HPA 轴和行为，并在可能影响成年期疾病风险的关键压力调节系统中建立性别差异。特别讨论了雄激素对已知在 HPA 和应激行为反应（促肾上腺皮质激素释放因子、加压素和催产素）中起关键作用的神经肽系统的影响。