The hypothalamus and limbic brain play an important role in the regulation of gonadotropin secretion and reproductive behavior in the male. Numerous pharmacological studies have suggested a major role for monoaminergic neurons in mediating aspects of both of these processes. There is, however, a complex interaction between androgens and neurotransmitters within the brain. Not only do changes in neurotransmission affect androgen-dependent processes, but changes in the levels of circulating testosterone can affect some processes relating to catecholamine transmission. This grant proposes to study these aspects of the cellular mechanism of androgen action by determining (1) whether monoamines affect the metabolism of androgens to active estrogenic metabolites (aromatization) in the brain; and (2) whether testosterone (T) or its active metabolites, in turn, regulate the number and/or affinity of dopamine (D2) receptors in regions of the brain relevant to behavioral and neuroendocrine functions. To accomplish the first objective, experiments are outlined that will measure aromatase activity and nuclear androgen receptor concentrations under conditions where monoamine dynamics have ben altered by agonists, antagonists, and synthesis blockers. The second goal will be approached with studies that will measure the binding parameters of dopamine (D2) receptors in male rats after various endocrine manipulations that will vary the androgen status on the animals. Pharmacologic intervention will be used to dissect out the contribution made by active T metabolites. Finally, studies are proposed which will begin to localize androgen modulated catecholamine binding within specific hypothalamic nuclei. This studies proposed herein will lead to a better understanding of how androgens interact with neurotransmitters to regulate neuronal functions. Moreover the information gained should add to our knowledge to the central components in the physiology and pathophysiology of male reproduction and sexual development. In a larger sense, this research has implications for our understanding of the cellular events underlying the action of all gonadal steroids
