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Inhibition of Hypothalamic Aromatase Activity by 5 Beta‐Dihydrotestosterone
Author(s) -
Schumacher M.,
Hutchison R. E.,
Hutchison J. B.
Publication year - 1991
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.1991.tb00266.x
Subject(s) - aromatase , dihydrotestosterone , medicine , endocrinology , testosterone (patch) , steroid , androgen , biology , chemistry , androstenediol , enzyme , hormone , dehydroepiandrosterone , biochemistry , cancer , breast cancer
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.