Inhibition of Hypothalamic Aromatase Activity by 5 Beta‐Dihydrotestosterone

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Abstract
A variable amount of circulating testosterone that reaches brain cells is converted to biologically inactive 5β-reduced metabolites, namely, 5β-dihydrotestosterone (5β-DHT) and 5β-androstane-3α,17β-diol (5β,3α-diol). In avian species, the production of inactive 5β-DHT and 5β,3α-diol is highest during embryonic and post-hatching life. In the present study, we have investigated the possibility that 5β-reduction may not only correspond to a steroid inactivation pathway, but that 5β-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, 5β-DHT but not 5β,3α-diol inhibits the activity of the aromatase enzyme, which converts testosterone to 17β-oestradiol. During the first days after hatching, when the production of 5β-reduced metabolites is high, the hypothalamic aromatase is also inhibited by 5β-DHT. We conclude that a high 5β-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.

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