A group of investigations are proposed regarding androgen secretion, metabolism, and action using hirsutism and related hyperandrogenic disorders as model states. The role of the adrenal gland in these disorders will be investigated. The hypothesis will be tested in vivo that the human corticotropin releasing hormone (CRH) test will better distinguish among premature or exaggerated adrenarche, mild or heterozygous forms of congenital adrenal hyperplasia and normal than will the ACTH test. The hypothesis will be tested that hypothalmo-pituitary-adrenal (HPA) axis recovery from protracted suppression by glucocorticoid will be better indicated by plasma dehydroepiandrosterone (DHA) than by cortisol or ACTH responsiveness to CRH. The hypothesis will be tested in vitro that the zona reticularis is the major source of the adrenarchal adrenal androgens, DHA and DHA sulfate, because of its unique pattern of pregnenolone metabolism. The hypothesis will be tested that polycystic ovary syndrome (PCOS) can arise from isolated ovarian steroidogenic defects. The incidence of defects in the ovarian steroidogenic pathway will be determined in PCOS patients. Apparent decreases in the efficiency of the steps in the biosynthesis of estradiol from pregnenolone will be identified by abnormal relationships among the plasma concentrations of steroid intermediates in response to gonadotropin releasing hormone agonist (GnRHa). Excessive LH and FSH responsiveness to GNRHa will be a criterion for ovarian secretory inefficiency. We also plan to investigate the mechanism of action of androgens upon the pilosebaceous apparatus (PSA). The hypothesis will be tested that hair matrix cells are induced to differentiate by dermal papilla cells and that androgens affect sexual hair growth by an indirect effect on the latter. The hypothesis will be similarly tested that androgens similarly stimulate sebaceous glands through an indirect effect on the enveloping mesenchymal cells. Steroids will be measured by radioimmunoassay (RIA) after high performance liquid chromatography. The secretory response to ACTH and metabolism by adrenocorticol zones will be tested by RIA and by double isotope techniques. Human sexual hairs and fibroblasts, rat vibrissae, and rat preputial glands will be studied using tissue and organ culture. Androgen metabolism and androgen receptor sites will be studied in these cultured PSA cells.
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