GONADOTROPIN REGULATION AND REPRODUCTION IN THE MALE

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Although it is well known that chronic adrenocortical activation will suppress reproductive function in rodents, little information exists on the precise actions of adrenocorticotropic hormone (ACTH) on the hypothalamic-pituitary-testicular axis. The studies outlined in this proposal will continue our investigations of adrenal-gonadal interactions in the male, examining the effects of ACTH administration in adult as well as in neonatal males. Studies conducted in a variety of species, including man, have shown that chronic ACTH treatment will suppress plasma testosterone levels. In contrast, the few studies which have investigated acute effects of ACTH administration to males have observed an elevation in circulating testosterone. Experiments will be conducted to examine both acute and chronic effects of controlled ACTH infusions in male rats. Measurements of hypothalamic LHRH content and the pituitary responsiveness to exogenous LHRH administration in these experiments, utilizing both intact and castrated, testosterone-treated males, should provide information about hypothalamic and pituitary effects of ACTH in the adult. In addition, effects of ACTH on testicular blood flow and responsiveness to hCG stimulation will be studied in order to evaluate effects of adrenocortical activation on testicular function. In neonatal males, we have previously shown that ACTH treatment for 3 days induced a persistent reduction in circulating FSH titers while not affecting plasma LH concentrations. This effect of ACTH is apparently not mediated via enhanced corticosterone secretion but can be mimicked, at least in part, by late postnatal (day 7 to 9) androgen administration. Studies will be conducted to determine which androgen is involved in this response and to evaluate possible alterations in the hypothalamic and pituitary control of gonadotropin secretion. Hypothalamic LHRH content and distribution, as well as blood flow to various regions of the brain will also be studied in animals showing alterations in gonadotropin regulation (i.e. early- and late- neonatally androgenized males and long-term castrated males). These experiments will evaluate the relative importance of various LHRH pathways in the regulation of pituitary FSH and LH secretion and will provide information about the role of hypothalamic blood flow in gonadotropin regulation.