GONADAL STEROID MODULATION OF BRAIN-PITUITARY FUNCTION

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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.