Reproductive Suppression by Cortisol at Pituitary Gland

糖皮质激素被认为在生殖功能抑制中起中介作用。 压力。皮质醇快速(&lt；30min)和慢性(&gt；48h)抑制绵羊搏动性的促黄体生成素分泌。此外， 去卵巢母羊的促黄体生成素抑制是通过降低垂体对促性腺激素释放激素的反应性而不是通过 减少GnRH的释放，并由II型糖皮质激素受体(GR)介导。基于这些发现， 我建议检验以下统一的假设：应激水平的皮质醇升高抑制脑下垂体 通过不同的快速和慢性抑制机制，直接在垂体对GnRH产生反应。这个 慢性效应是由细胞内II型GR通过减少的GnRH受体介导的，而快速效应是通过GnRH受体减少而实现的 是由膜结合的II型GR介导的，并且不依赖于这种抑制而发生。要解决这个问题 假设，提出了三个目标：1)皮质醇是否直接作用于脑下垂体以降低反应性 对GnRH？2)是由膜结合的II型GR介导的皮质醇的快速抑制作用，而 细胞内II型GR介导的慢性抑制效应与皮质醇的慢性效应相关 随着GnRH受体mRNA和蛋白水平的降低，以及不依赖这些影响的快速效应？

Glucocorticoids are considered to play a mediatory role in the suppression of reproductive function during stress. Cortisol rapidly (<30min) and chronically (>48 h) inhibits pulsatile LH secretion in ewes. Further, the inhibition in LH in ovariectomized ewes occurs via reduced pituitary responsiveness to GnRH, not via reduced GnRH release and is mediated by the type II glucocorticoid receptor (GR). Based on these findings, I propose to test the following unifying hypothesis: Elevations in stress levels of cortisol suppress pituitary responsiveness to GnRH directly at the pituitary via distinct rapid and chronic inhibitory mechanisms. The chronic effect is mediated by an intracellular type II GR via reduced GnRH receptors whereas the rapid effect is mediated by a membrane-bound type II GR and occurs independent of this inhibition. To address this hypothesis, three aims are proposed: 1) Does cortisol act directly upon the pituitary to reduce responsiveness to GnRH? 2) Is the rapid inhibitory effect of cortisol mediated by a membrane-bound type II GR and the chronic inhibitory effect mediated by an intracellular type II GR? 3) Is the chronic effect of cortisol associated with reduced levels of GnRH receptor mRNA and protein and the rapid effect independent of these effects?