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GONADAL STEROID MODULATION OF BRAIN-PITUITARY FUNCTION

性腺类固醇对脑垂体功能的调节

基本信息

批准号：
3321632
负责人：
William J Millard
金额：
$ 7.86万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-04-01 至 1991-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3321632
关键词：
gonadotropins hypothalamus somatostatin

项目摘要

The modulatory role of gonadal steroids in regulating sex- dependent growth hormone (GH) secretion will be studied during development through reproductive senescence. A series of interrelated experimental approaches will be used to clarify the level of gonadal steroid control of GH secretion (hypothalamic, pituitary and peripheral organs). In the course of these studies, GH secretory patterns throughout life in the rat will be defined. We anticipate that the results of these studies will advance our understanding of the development and maintenance of GH secretory dynamics and help explain sex-related differences in growth rates. The first series of experiments will define both a dose-response and time course for gonadal steroid action on GH secretory patterns using a chronically-cannulated rate in vivo model. Direct pituitary effects of steroids will be assessed by observing the GH response to GH-relating factor (GRF). A second series of experiments will investigate the hypothesis that gonadal steroids modulate GH secretion via a novel mechanism termed a "steroid sensitive switch". The existence of the "steroid sensitive switch" in adult rats will be studied by utilizing a paradigm involving the exposure of male and female rats to alternating courses of steroids. In addition, the development of the "steroid sensitive switch" will be studied beginning with gestational life through adulthood. A third series of experiments will focus on GH secretory patterns throughout the life of male and female rats. Studies will investigate GH secretory patterns during puberty, during the estrous cycle in adult female rats and during various stages of reproductive senescence in both male and female rats. Studies will extend to investigating GRF-induced GH secretion during these various stages of life. Finally, the metabolic clearance rate and half-life components of GH in male and female rats will be determined to establish whether gonadal steroids play a role in modulating these parameters.

性腺类固醇在性调节中的调节作用- 将在研究期间研究依赖性生长激素（GH）分泌通过生殖衰老而发育。一系列相关的实验方法将被用来澄清 GH分泌的性腺类固醇控制水平（下丘脑，垂体和外周器官）。在这些研究的过程中，将定义大鼠一生中GH的分泌模式。我们预计，这些研究的结果将推动我们的了解生长激素的发育和维持分泌动力学和帮助解释性别相关的差异，增长率。第一系列的实验将定义剂量反应性腺类固醇激素对GH分泌的作用和时间过程使用慢性插管率体内模型的模式。类固醇的直接垂体效应将通过观察 GH对GH相关因子（GRF）反应。第二系列的实验将调查这一假设性腺类固醇通过一种新的这一机制被称为“类固醇敏感开关”。的存在成年大鼠中的“类固醇敏感开关”将通过利用一个范例，涉及男性和女性的暴露，大鼠交替服用类固醇此外该将研究开发“类固醇敏感开关” 从妊娠期到成年期第三个系列的实验将集中在生长激素分泌模式在雄性和雌性大鼠的一生中。研究将研究生长激素分泌模式在青春期，在成年雌性大鼠的发情周期和雄性和雌性大鼠的生殖衰老。研究将扩展到研究GRF诱导的GH分泌，这些不同的人生阶段。最后，测定了代谢清除率和半衰期组分，将测定雄性和雌性大鼠的GH，以建立性腺类固醇是否在调节这些参数