Male pseudohermaphrodites, particularly subjects with 5 alpha- reductase deficiency and androgen insensitivity are unique experiments of nature to elucidate the differential effects of testosterone (T) and dihydrotestosterone (DHT) in male sexual differentiation and development as well as other androgen mediated physiologic parameters. The proposed studies of these subjects include; evaluation of the differential effect of T and DHT in the negative feedback control of LH secretion through studies of the pulsatile gonadotrophin secretory profile; definition of the roles of T and DHT in the formation of male gender identity, elucidation of the roles of T and DHT (prenatally and postnatally) on observed sex differences in cognition and lateralization; and definition of the role of DHT on sexual potency in the male. Further animal studies with potent competitive azasteroid inhibitors of the enzyme 5 alpha-reductase to decrease DHT production are planned to further delineate the differential effects of the biologic roles of testosterone and dihydrotestosterone in male sexual differentiation and development. Comparison studies will be carried out with the antiandrogen, flutamide, which blocks the action of both T and DHT. The current proposal includes further studies to define the roles of T and DHT in differentiation of the prostate; the cyclical release of gonadotrophins, spermatogenesis, testicular descent; and sexual behavior of the rat. Studies also include evaluation of the effect of 5 alpha-reductase deficiency on sexual differentiation in the rabbit with particular attention toward defining the role of T and DHT in differentiation of the Wolffian ducts and prostatic differentiation.
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