INHIBITION OF HYPOTHALAMIC AROMATASE-ACTIVITY BY 5BETA-DIHYDROTESTOSTERONE

A variable amount of circulating testosterone that reaches brain cells is converted to biologically inactive 5-beta-reduced metabolites, namely, 5-beta-dihydrotestosterone (5-beta-DHT) and 5-beta-androstane-3-alpha, 17-beta-diol (5-beta,3-alpha-diol). In avian species, the production of inactive 5-beta-DHT and 5-beta,3-alpha-diol is highest during embryonic and post-hatching life. In the present study, we have investigated the possibility that 5-beta-reduction may not only correspond to a steroid inactivation pathway, but that 5-beta-reduced metabolites of testosterone may exert direct inhibitory effects on enzymatic pathways producing biologically active steroids. When added to hypothalamic homogenates prepared from adult male doves, 5-beta-DHT but not 5-beta,3-alpha-diol inhibits the activity of the aromatase enzyme, which converts testosterone to 17-beta-oestradiol. During the first days after hatching, when the production of 5-beta-reduced metabolites is high, the hypothalamic aromatase is also inhibited by 5-beta-DHT. We conclude that a high 5-beta-reductase activity during sensitive periods for sexual differentiation may protect the avian brain from the differentiating effects of circulating androgens by inhibiting the production of oestrogen.