Estrogen potentiates adrenocortical responses to stress in female rats
Estrogen potentiates adrenocortical responses to stress in female rats
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DOI：
10.1152/ajpendo.00102.2006
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发表时间：
2007-04-01
影响因子：
5.1
通讯作者：
Herman, James P.
中科院分区：
文献类型：
--
作者：
Figueiredo, Helmer F.;Ulrich-Lai, Yvonne M.;Herman, James P.
雌激素增强雌性大鼠肾上腺皮质对应激的反应。Am J Physiol Endocrinol Metab 292：E1173-E1182，2007。首次发表于2006年12月19日; doi：10.1152/ajpendo.00102.2006。- 众所周知，雌激素显著增强女性对急性应激的糖皮质激素反应。然而，对这种调节的确切机制知之甚少。在这里，我们测试是否雌激素增强室旁核（PVN）的激活下丘脑通过测量应激诱导的c-fos mRNA表达的限制应激卵巢切除（OVX）大鼠生理相关剂量的雌二醇（E-2），主要的女性雌激素治疗的PVN。正如预期的那样，E-2增强血浆皮质酮反应的限制OVX女性。然而，E-2显着减弱应激诱导的c-fos基因在PVN的表达和抑制血浆ACTH反应在这些动物。此外，E-2-抑制作用被单独的孕酮（P）或与E-2的组合所模拟。有趣的是，E-2和P的抑制性中枢效应显然独立于基础室旁促肾上腺皮质激素释放激素（CRH）的转录，因为这些卵巢类固醇激素并没有显着影响PVN CRH mRNA的表达在非应激大鼠。这些意想不到的发现表明，E2通过额外的外周（即，肾上腺）机制。事实上，E-2显着增强血浆皮质酮反应和肾上腺皮质酮含量地塞米松阻断OVX大鼠挑战不同剂量的外源性ACTH。这些结果表明，增强肾上腺对ACTH的敏感性是一个重要的生理机制介导的E-2相关的糖皮质激素分泌过多的压力女性。
Estrogen potentiates adrenocortical responses to stress in female rats. Am J Physiol Endocrinol Metab 292: E1173-E1182, 2007. First published December 19, 2006; doi:10.1152/ajpendo.00102.2006. - It is well established that estrogens markedly enhance the glucocorticoid response to acute stress in females. However, the precise mechanism responsible for this regulation is poorly understood. Here, we tested whether estrogens enhance the activation of the paraventricular nucleus (PVN) of the hypothalamus by measuring stress-induced c-fos mRNA expression in the PVN of restraint-stressed ovariectomized (OVX) rats treated with physiologically relevant doses of estradiol (E-2), the major female estrogen. As expected, E-2 enhanced plasma corticosterone responses to restraint in OVX females. However, E-2 markedly attenuated the stress-induced c-fos gene expression in the PVN and inhibited plasma ACTH responses in these animals. Furthermore, E-2-inhibitory effects were mimicked by progesterone (P) alone or in combination with E-2. Interestingly, the suppressive central effects of both E-2 and P were apparently independent of basal paraventricular corticotropin-releasing hormone (CRH) transcription, since these ovarian steroids did not significantly affect PVN CRH mRNA expression in unstressed rats. These unexpected findings suggested that E2 promotes glucocorticoid hypersecretion in females by additional peripheral (i.e., adrenal) mechanisms. Indeed, E-2 markedly enhanced plasma corticosterone responses and adrenal corticosterone content in dexamethasone-blocked OVX rats challenged with varying doses of exogenous ACTH. These results suggest that enhanced adrenal sensitive to ACTH is an important physiological mechanism mediating E-2-related glucocorticoid hypersecretion in stressed females.