Development of testosterone-metabolizing pathways in the avian brain: enzyme localization and characteristics.

Metabolites formed from testosterone in the brain, their neuroanatomical distribution and the kinetic properties of the enzymes were studied in male and female Japanese quail chicks and compared with the adult brain using an in vitro radioassay. Oestradiol-17 beta. 5 alpha-dihydrotestosterone, 5 beta-dihydrotestosterone and 5 beta-androstane-3 alpha, 17 beta-diol were identified as metabolites of testosterone (T) in hypothalamic samples of 3-day-old quail. Estimation of the Km of hypothalamic aromatase (4.8 X 10(-8) M) and 5 alpha-reductase (11.8 X 10(-8) M) suggests that the affinities of the enzymes for substrate (T) are similar to those of comparable adult brain enzymes. Formation of 5 alpha-dihydrotestosterone and oestradiol-17 beta was higher in the preoptic area and posterior hypothalamus than either the area basalis or neostriatum intermediale, whereas 5 beta-dihydrotestosterone yield did not differ between brain areas. Similar regional differences in testosterone metabolism were confirmed for the developing dove brain (2-8-day-old chicks). In both quail and dove, the activities of hypothalamic aromatase and 5 alpha-reductase were lower in the chick brain than in the adult, but brain 5 beta-reductase activity was much higher during early development than in adulthood. We conclude that the major pathways of testosterone metabolism in the brain are active during early development. Concentrations of enzymes and relative differences in enzyme activity between brain areas change substantially during development.