Metabolic control of the behavioural action of androgens in the dove brain: testosterone inactivation by 5 beta-reduction.
In vitro studies of androgen metabolism in the dove brain show that testosterone is rapidly converted to 5 beta-reduced metabolites (5 beta-dihydrotestosterone and the two corresponding 3 alpha/3 beta diols). The preoptic region and the anterior ventromedial and posterior hypothalamus which are target areas for androgen action on behaviour and the neuroendocrine system show significantly less 5 beta-reduction than adjacent parolfactory, septal and striatal areas not directly involved in androgen action. In contrast to 5 alpha-reduction and aromatization, which lead to the formation of active metabolites in the dove brain, 5 beta-reduction is likely to be part of a testosterone (T) inactivation mechanism because: (a) intrahypothalamic implants of 5 beta-dihydrotestosterone were ineffective for male behaviour in the dove; (b) 5 beta-reduced metabolites of T were not detected in hypothalamic cell nuclei following intramuscular injection of tritiated testosterone, and were rapidly eliminated from brain cells; (c) the 4 beta-diols were also found to be a major product of T catabolism in the liver, a site of androgen inactivation. Long-term androgen deficit induced by castration increased 5 beta DHT formation in the preoptic area, but not in an adjacent parolfactory area. The increase was reversed by exogenous testosterone and oestradiol-17 beta indicating that the 5 beta-reduction pathway in an androgen-sensitive brain area is influenced by hormonal conditions. It is suggested that 5 beta-reduction is a testosterone inactivation pathway involved in the regulation of brain sensitivity to androgens.
D015113:Androstane-3,17-diol / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D010856:Columbidae; D013196:Dihydrotestosterone / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D012726:Sexual Behavior, Animal / Q000502:physiology*; D013739:Testosterone / Q000378:metabolism*
D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D013739:Testosterone; D004958:Estradiol