title: Androgen metabolism by hepatic and renal tissues of the fetal rhesus monkey.
abstract: 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 5 beta-androstane-3 alpha,17 beta-diol (5 beta-diol) at 0 degrees C as at 4 degrees-45 degrees C without exogenous cofactors. The principal product formed from 5 alpha-dihydrotestosterone (5 alpha-DHT) was 5 alpha-diol. A 1000-fold molar excess of radioinert 5 beta- or 5 alpha-DHT inhibited 5 beta-diol formation from [3H]T by cytosols and increased 5 beta-DHT formation. Similarly, using 5 alpha-DHT as substrate, 5 alpha-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 5 beta-reduced products from [3H]T in the presence of an NADPH generating system whereas kidney homogenates produced 5 alpha-reduced products. These data provide new information on the capacity of fetal monkey liver and kidney to metabolize androgens. The 3 alpha-reductases are cytosolic. The 5 alpha- and 5 beta-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 5 alpha-DHT is the active androgen in fetal liver since testosterone is metabolized to 5 beta-DHT and 5 beta-diol which are inactive androgens.
authors.affiliation: Department of Physiology, School of Medicine, Oregon Health Sciences University, Portland 97201.
authors.forename: J A
authors.initials: JA
authors.lastname: Resko
authors.forename: S E
authors.initials: SE
authors.lastname: Abdelgadir
authors.forename: P B
authors.initials: PB
authors.lastname: Connolly
mesh_terms: D000818:Animals; D002458:Cell Fractionation; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000196:embryology / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D013696:Temperature; D013739:Testosterone / Q000378:metabolism*
chemical_list: D013196:Dihydrotestosterone; D013739:Testosterone; D009249:NADP