CENTRAL GLUCOCORTICOID CONTROL OF PITUITARY LH RELEASE

虽然糖皮质激素过量的生理和药理状态， 包括压力，一直以来都与 老鼠和其他物种的生殖内分泌功能， 糖皮质激素抑制下丘脑的作用机制(S)和部位(S) 目前对垂体促黄体生成素(LH)轴的认识尚不清楚。而当 很少有研究调查糖皮质激素可能会 通过神经内分泌机制抑制黄体生成素的释放， 这些激素已经在大鼠体内离散的神经部位被识别出来 大脑，最近被定位于特定的下丘脑核团 已经与控制脑下垂体促黄体生成素的释放有关。结果来自 初步数据研究表明，脑室(ICV) 使用一种有效的糖皮质激素受体激动剂可以促进 正常成年男性血液中促黄体生成素水平的剂量比例下降 老鼠。这些数据表明，中枢糖皮质激素受体介导 对促黄体生成素释放的抑制作用，并提示这些受体可能 存在于影响神经内分泌调节的神经通路中 脑垂体促黄体生成素。以下建议中概述的研究将寻求 确定起作用的中枢糖皮质激素受体的类型(S) 抑制黄体生成素的释放。将进行研究以调查影响 脑室注射高选择性激动剂的分级剂量 高亲和力I型和低亲和力II型糖皮质激素受体 对雄性大鼠外周血浆黄体生成素水平的影响。平行研究将 评价这些受体亚型对生理学的意义 通过研究激素释放的影响来调节激素释放 特异性受体阻断基础和应激刺激的促黄体生成素释放。 基于全球药物操作的观察结果 糖皮质激素受体种群，我们将利用已发表的信息 关于糖皮质激素受体亚型在脑内的微观分布 大鼠脑给药选择性受体激动剂离散脑 网站，以努力描述神经解剖学分布的特点 调节脑下垂体促黄体生成素释放下降的糖皮质激素受体。 最后，将进行免疫细胞化学分析以确定 视前区和下丘脑是否存在糖皮质激素受体 结合免疫系统中存在的黄体生成素受体- 含有释放激素(LHRH)的神经元成分。

Although physiologic and pharmacologic states of glucocorticoid excess, including stress, have been consistently correlated with diminished reproductive endocrine function in the rat and other species, the mechanism(s) and site(s) of glucocorticoid inhibition of the hypothalamic- pituitary luteinizing hormone (LH) axis are not clearly understood. While few studies have investigated the possibility that glucocorticoids may suppress LH release via a neuroendocrine mechanism, specific receptors for these hormones have been identified in discrete neural sites within the rat brain, and have been localized recently within specific hypothalamic nuclei already implicated in the control of pituitary LH release. Results from preliminary data studies indicate that intracerebroventricular (icv) administration of a potent glucocorticoid receptor agonist can promote a dose-proportionate decline in circulating LH levels in intact adult male rats. These data indicate that central glucocorticoid receptors mediate a suppressive effect upon LH release, and suggest that such receptors may exist within neural pathways that influence neuroendocrine regulation of pituitary LH. The studies outlined in the following proposal will seek to identify the type(s) of central glucocorticoid receptor that serves to inhibit LH release. Studies will be undertaken to investigate the effects of icv administration of graded doses of highly selective agonists of the high affinity type I and the low affinity type II glucocorticoid receptor on peripheral plasma LH levels in the male rat. Parallel studies will evaluate the significance of these receptor subtypes to the physiological regulation of hormone release through investigation of the effects of specific receptor blockade on basal and stress-stimulated LH release. Based upon observed results of global pharmacologic manipulation of glucocorticoid receptor populations, we will utilize published information concerning the microdistribution of glucocorticoid receptor subtypes in the rat brain to administer selective receptor agonists to discrete brain sites, in an effort to characterize the neuroanatomical distribution of glucocorticoid receptors that mediate a decline in pituitary LH release. Lastly, immunocytochemical analyses will be carried out to determine whether glucocorticoid receptors within the preoptic area and hypothalamus bind to receptors present within immunodemonstrable luteinizing hormone- releasing hormone (LHRH)-containing neuronal elements.