Inhibition of hypothalamic aromatase activity by 5 Beta-dihydrotestosterone

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