A role for the androgen metabolite, 5alpha-androstane-3beta,17beta-diol, in modulating oestrogen receptor beta-mediated regulation of hormonal stress reactivity.
A role for the androgen metabolite, 5alpha-androstane-3beta,17beta-diol, in modulating oestrogen receptor beta-mediated regulation of hormonal stress reactivity.
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DOI：
10.1111/j.1365-2826.2009.01840.x
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发表时间：
2009-03
影响因子：
3.2
通讯作者：
Zuloaga DG
中科院分区：
文献类型：
--
作者：
Handa RJ;Weiser MJ;Zuloaga DG
下丘脑-垂体-肾上腺（HPA）轴的激活是动物对威胁稳态的环境扰动的基本反应。这些反应由下丘脑室旁核（PVN）中合成和分泌促肾上腺皮质激素释放激素（CRH）的神经元调节。其他PVN神经肽，如精氨酸加压素和催产素，也可以调节PVN中CRH神经元的活性，并增强垂体前叶的CRH促分泌活性。在啮齿类动物中，HPA反应性的性别差异是明确的;女性在应激后表现出比男性更强的HPA轴激活。这些性别差异主要是由于性类固醇激素，睾酮和雌激素，对HPA功能的相反作用。Ostreogen增强应激激活的促肾上腺皮质激素（ACTH）和皮质酮（CORT）的分泌，而睾酮降低HPA轴的增益并抑制ACTH和CORT对应激的反应。数据显示，雄激素可通过涉及雌激素受体（ER）β的新途径直接作用于雄性大鼠PVN神经元，而雌激素主要通过ERα发挥作用。因此，我们检验了这样的假设，即在男性中，睾酮通过结合ERβ的雄激素代谢物抑制HPA功能。这种新作用的神经生物学机制的线索可以从显示ERβ在PVN含催产素细胞中广泛共定位的研究中收集。因此，在这篇综述中，我们讨论了睾酮通过代谢为5α-雄甾烷-3 β，17 β-二醇抑制HPA反应性的可能性，5 α-雄甾烷-3 β，17 β-二醇是一种结合ERβ并调节PVN含催产素神经元的化合物。这些发现表明，重新评估研究雄激素受体信号通路。
Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a basic response of animals to environmental perturbations that threaten homeostasis. These responses are regulated by neurones in the paraventricular nucleus of the hypothalamus (PVN) that synthesise and secrete corticotrophin-releasing hormone (CRH). Other PVN neuropeptides, such as arginine vasopressin and oxytocin, can also modulate activity of CRH neurones in the PVN and enhance CRH secretagogue activity of the anterior pituitary gland. In rodents, sex differences in HPA reactivity are well established; females exhibit a more robust activation of the HPA axis after stress than do males. These sex differences primarily result from opposing actions of sex steroids, testosterone and oestrogen, on HPA function. Ostreogen enhances stress activated adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) secretion, whereas testosterone decreases the gain of the HPA axis and inhibits ACTH and CORT responses to stress. Data show that androgens can act directly on PVN neurones in the male rat through a novel pathway involving oestrogen receptor (ER)β, whereas oestrogen acts predominantly through ERα. Thus, we examined the hypothesis that, in males, testosterone suppresses HPA function via an androgen metabolite that binds ERβ. Clues to the neurobiological mechanisms underlying such a novel action can be gleaned from studies showing extensive colocalisation of ERβ in oxytocin-containing cells of the PVN. Hence, in this review, we address the possibility that testosterone inhibits HPA reactivity by metabolising to 5α-androstane-3β,17β-diol, a compound that binds ERβ and regulates oxytocin containing neurones of the PVN. These findings suggest a re-evaluation of studies examining pathways for androgen receptor signalling.
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影响因子：
--
作者：
Bauman, DR;Steckelbroeck, S;Penning, TM
通讯作者：
Penning, TM
DOI：
10.1073/pnas.95.6.3281
发表时间：
1998-03-17
影响因子：
11.1
作者：
Alves, SE;Lopez, V;Weiland, NG
通讯作者：
Weiland, NG
影响因子：
4.1
作者：
BINGAMAN, EW;MAGNUSON, DJ;HANDA, RJ
通讯作者：
HANDA, RJ
影响因子：
4.8
作者：
Hrabovszky, E;Kalló, I;Liposits, Z
通讯作者：
Liposits, Z
影响因子：
4.8
作者：
HANDA, RJ;STADELMAN, HL;RESKO, JA
通讯作者：
RESKO, JA