Enzymatic oxidation and reduction of C19-delta5-3beta-hydroxysteroids by hepatic microsomes. V. Testosterone as a neonatal determinant in rats of the 7- and 16alpha-hydroxylation and reduction of 3beta-hydroxyandrost-5-en-17-one (DHA).
The oxido-reductive metabolism of [14C]dehydroepiandrosterone (DHA) by hepatic microsomes from 40- or 70-day-old rats of either sex castrated neonatally has been compared after several treatment regimens with testosterone propionate (TP). The low transformation rate of DHA to 16-oxygenated metabolites produced by neonatal orchiectomy (0.09 +/- 0.04 nmoles min-1 mg-1), was not restored in 70-day-old males by either neonatal or pubertal treatment with TP. The rates were only partially restored (0.74 +/- 0.44) toward nromal adult levels (1.30 +/- 0.16) by the combination of neontal and pubertal treatments, in increments that maintained normal body weight but produced no visible growth of the male accessory glands. The combination of neonatal and pubertal treatments with larger doses of TP enough to produce normal accessory gland growth, stimulated the enzymatic rates of 16alpha-7alpha-, or 7beta-hydroxylases to levels that exceeded those of intact adult males. In 40-day-old males, the 16-oxygenation rate was restored by the latter regimen, but only to the levels characteristic of yound males (0.56 +/- 0.24), and young females responded more (1.03 +/- 0.33) than the males. The 7-oxygenation rate of DHA responded in both age groups to smaller doses of TP than did that of the 16-oxygenation. None of these manipulations altered the reduction of DHA to androst-5-ene-3bets-17beta-diol. We conclude that testosterone activates hepatic DHA hydroxylases in pubertal male rats only if neonatal imprinting by testosterone preceeds the subsequent stimulus. In addition, the DHA 16alpha-hydroxylase of young males is less sensitive than that of young females, but this pattern is reversed by 70 days of age. The hepatic males are both sensitive to testosterone, but the response of the glands is diminished by age.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D005260:Female; D006914:Hydroxysteroids / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000254:growth & development; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010053:Ovary / Q000502:physiology; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects; D051381:Rats; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013737:Testis / Q000502:physiology; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology*
D006914:Hydroxysteroids; D013739:Testosterone; D003687:Dehydroepiandrosterone; D013250:Steroid Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase