PDF(Pubmed)
Abstract：
Gonadal hormone actions through androgen receptor (AR) and estrogen receptor alpha (ERα) regulate sex differences in hypothalamic-pituitary-adrenal (HPA) axis responsivity and stress-related behaviors. Here we tested whether corticotropin releasing factor (CRF) expressing neurons, which are widely known to regulate neuroendocrine and behavioral stress responses, co-express AR and ERα as a potential mechanism for gonadal hormone regulation of these responses. Using Crh-IRES-Cre::Ai9 reporter mice we report high co-localization of AR in CRF neurons within the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BST), medial amygdala (MeA), and ventromedial hypothalamus (VMH), moderate levels within the central amygdala (CeA) and low levels in the paraventricular hypothalamus (PVN). Sex differences in CRF/AR co-expression were found in the principal nucleus of the BST (BSTmpl), CeA, MeA, and VMH (males>females). CRF co-localization with ERα was generally lower relative to AR co-localization. However, high co-expression was found within the MPOA, AVPV, and VMH, with moderate co-expression in the arcuate nucleus (ARC), BST, and MeA and low levels in the PVN and CeA. Sex differences in CRF/ERα co-localization were found in the BSTmpl and PVN (males>females). Finally, we assessed neural activation of CRF neurons in restraint-stressed mice and found greater CRF/c-Fos co-expression in females in the BSTmpl and periaqueductal gray, while co-expression was higher in males within the ARC and dorsal CA1. Given the known role of CRF in regulating behavioral stress responses and the HPA axis, AR/ERα co-expression and sex-specific activation of CRF cell groups indicate potential mechanisms for modulating sex differences in these functions.
摘要：
通过雄激素受体（AR）和雌激素受体α（ERα）的性腺激素作用调节下丘脑-垂体-肾上腺（HPA）轴反应性和应激相关行为的性别差异。在这里，我们测试了促肾上腺皮质激素释放因子（CRF）是否表达神经元，众所周知，它们可以调节神经内分泌和行为应激反应，共表达AR和ERα作为性腺激素调节这些反应的潜在机制。使用Crh-IRES-Cre::Ai9报告小鼠，我们报告了内侧视前区（MPOA）内CRF神经元中AR的高度共定位，终末纹床核（BST），杏仁核内侧(MeA),和腹内侧下丘脑（VMH），杏仁核中央（CeA）内的中等水平和室旁下丘脑（PVN）中的低水平。在BST（BSTmpl）的主核中发现了CRF/AR共表达的性别差异，CeA,MeA,和VMH（男性>女性）。CRF与ERα的共定位相对于AR共定位通常较低。然而,在MPOA中发现了高共表达，AVPV,和VMH,在弓状核（ARC）中适度共表达，BST,和MeA和低水平的PVN和CeA。在BSTmpl和PVN中发现了CRF/ERα共定位的性别差异（男性>女性）。最后,我们在束缚应激小鼠中评估了CRF神经元的神经激活，并在BSTmpl和导水管周围灰中发现了更大的CRF/c-Fos共表达。而男性在ARC和背侧CA1中的共表达较高。鉴于CRF在调节行为应激反应和HPA轴方面的已知作用，AR/ERα共表达和CRF细胞组的性别特异性激活表明了调节这些功能中性别差异的潜在机制。
