Preliminary studies hae shown that the treatment of male rats with adrenocorti-cotropic hormone (ACTH) during the early postnatal period will result in a permanent and selective suppression of circulating FSH levels in the adult. The studies outlined in this proposal are designed to investigate the etiology of this reduction in serum FSH levels and to acquire more information about the neuroendocrine control systems which regulate the pituitary secretion of FSH in males. The timing and dose of postnatal ACTH or glucocorticoid treatment on gonadotropin regulation will be studied and the developmental periods which show maximum susceptibility for FSH alterations delineated. A detailed histological analysis of the testis will be conducted in males which exhibit chronic FSH suppression. Alterations in spermatogenesis and/or cellular morphology will indicate the effects of postnatal adrenocortical activation and will suggest possible sites of production for substance(s) responsible for the selective reduction in pituitary FSH secretion. Circulating levels of gonadal steroids and pituitary gonadotropins will be monitored by radioimmunoassay in normal males and males exhibiting altered FSH regulation. In addition, conrolled release devices will be used to maintain physiologically effective levels of estradiol and/or testosterone in gonadectomized animals. The relatively constant release rates of these devices will permit the investigation of steady-state interactions between testosterone and estradiol in the regulation of gonadotropin secretion. In addition, studies are planned on the role of hypothalamic blood flow in the negative feedback control of hypothalamic LHRH and pituitary gonadotropin secretion. Effects of neonatal ACTH on hypothalamic blood flow and LHRH will also be examined.
