Androgen metabolism by hepatic and renal tissues of the fetal rhesus monkey

Liver and kidney from fetal monkeys (day 125 of gestation) were fractionated into low speed pellets, microsomal and cytosolic fractions. Liver cytosols converted as much testosterone (T) to 5β-androstane-3α,17β-diol (5β-diol) at 0°C as at 4°–45°C without exogenous cofactors. The principal product formed from 5α-dihydrotestosterone (5α-DHT) was 5α-diol. A 1000-fold molar excess of radioinert 5β- or 5α-DHT inhibited 5β-diol formation from [ 3H]T by cytosols and increased 5β-DHT formation. Similarly, using 5α-DHT as substrate, 5α-diol formation was inhibited. Microsomal and low speed pellets with added cofactors formed products which recrystallized with either etiocholanolone or androsterone from [ 3H]T or [ 3H]DHT, respectively. Little product was formed without cofactor. Whole liver homogenates produced 5β-reduced products from [ 3H]T in the presence of an NADPH generating system whereas kidney homogenates produced 5α-reduced products. These data provide new information on the capacity of fetal monkey liver and kidney to metabolize androgens. The 3α-reductases are cytosolic. The 5α- and 5β-reductases are mostly in the low speed pellet but are sufficiently represented in cytosols to mediate diol formation. The 17-hydroxysteroid dehydrogenases are in the microsomal fraction. Our results suggest that 5α-DHT is the active androgen in fetal liver since testosterone is metabolized to 5β-DHT and 5β-diol which are inactive androgens.