description) The mammalian epididymis, the site of functional maturation of immature testicular spermatozoa, is under androgen control by 5alpha-reduced metabolites of testosterone. The enzyme, 4-ene-steroid 5alpha-reductase, converts testosterone to dihydrotestosterone. Two genes encode two 5alpha-reductase isozymes (types 1 and 2). In addition to androgen regulation, efferent duct ligation suggests modulation of epididymal 5alpha-reductase by other testicular factors. Activin and inhibin, two testicular factors, have opposing actions on 5alpha-reductase in cultured genital skin fibroblasts. Their actions on 5alpha-reductase gene expression within the epididymis is the basis for this proposal. The 5alpha-reductase gene expression is species and tissue specific, yet ethical constraints and unavailable normal human epididymal tissue precludes the practical study in man. The cynomolgus monkey (Macaca fascicularis), a nonhuman primate is the preferred animal model to study. The proposed hypothesis is: activin and inhibin, by opposing actions and in concert with androgens, modulate 5alpha-reductase gene expression in the primate proximal caput epididymis with minimal effect on the more distal corpus region.
