GONADAL STEROID MODULATION OF BRAIN-PITUITARY FUNCTION

性腺类固醇在调节性方面的调节作用-- 依赖性生长激素(GH)的分泌将在 通过生殖衰老进行发育。一系列 相关的实验方法将被用来澄清 性腺类固醇激素对生长激素分泌的控制水平(下丘脑、 垂体和外周器官)。在这些研究过程中， 将确定大鼠一生中GH的分泌模式。 我们预计，这些研究的结果将推动我们的 对GH的开发和维护的认识 分泌动态，并有助于解释性别相关的差异 增长率。 第一系列实验将定义两个剂量反应 性腺激素对生长激素分泌作用的时程 在活体模型中使用慢性插管率的模式。 类固醇的直接脑下垂体效应将通过观察来评估 生长激素对生长激素相关因子(GRF)的反应。 第二系列实验将对这一假设进行调查 性腺类固醇通过一种新的方式调节生长激素的分泌 这一机制被称为“类固醇敏感开关”。的存在 将对成年大鼠的“类固醇敏感开关”进行研究 利用一种涉及男性和女性暴露的范式 大鼠服用交替疗程的类固醇。此外， 将研究开发“类固醇敏感开关” 从妊娠期到成年期。 第三系列实验将集中在生长激素的分泌模式上 在雄鼠和雌鼠的一生中。研究将会 研究青春期、青春期和青春期生长激素的分泌模式 成年雌性大鼠的发情周期及其不同时期的发情 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 生命的这些不同阶段。 最后，新陈代谢清除率和半衰期成分 雄性和雌性大鼠的生长激素将被确定为 性腺类固醇是否在调节这些方面起作用 参数。

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.