CENTRAL GLUCOCORTICOID CONTROL OF PITUITARY LH RELEASE

中枢糖皮质激素控制垂体 LH 释放

• 批准号: 3242880
• 负责人: KAREN P BRISKI
• 金额: $ 5.67万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3242880
• 关键词: adrenergic receptor; corticosteroid receptors; corticosterone; dexamethasone; hormone regulation /control mechanism; hypothalamus; immunocytochemistry; inhibitor /antagonist; laboratory rat; luteinizing hormone; male; neuroanatomy; neuropeptide Y; neuropeptide receptor; norepinephrine; preoptic areas; stimulant /agonist

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.

尽管糖皮质激素过量的生理和药理状态， 包括压力在内，一直与减少相关 大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机制和位点 垂体黄体生成素（LH）轴尚不清楚。 尽管 很少有研究调查糖皮质激素可能 通过神经内分泌机制抑制 LH 释放，特定受体 这些激素已在大鼠体内离散的神经部位被发现 大脑，最近已定位于特定的下丘脑核团内 已经涉及垂体 LH 释放的控制。 结果来自 初步数据研究表明，脑室内 (icv) 给予有效的糖皮质激素受体激动剂可以促进 完整成年男性循环 LH 水平呈剂量比例下降 老鼠。 这些数据表明中枢糖皮质激素受体介导 对 LH 释放的抑制作用，并表明此类受体可能 存在于影响神经内分泌调节的神经通路中 垂体 LH。 以下提案中概述的研究将寻求 确定中枢糖皮质激素受体的类型 抑制 LH 释放。 将进行研究以调查其影响 梯度剂量的高选择性激动剂的ICV给药 高亲和力 I 型和低亲和力 II 型糖皮质激素受体 雄性大鼠外周血浆 LH 水平的影响。 平行研究将 评估这些受体亚型对生理学的重要性 通过研究影响来调节激素释放 对基础和应激刺激的 LH 释放的特异性受体阻断。 基于全球药理学操作的观察结果 糖皮质激素受体群体，我们将利用已发布的信息 关于糖皮质激素受体亚型的微观分布 大鼠大脑向离散大脑施用选择性受体激动剂 位点，以努力描述神经解剖学分布的特征 糖皮质激素受体介导垂体 LH 释放下降。 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有糖皮质激素受体 与免疫可证明的黄体生成激素中存在的受体结合- 含有释放激素（LHRH）的神经元元件。