Cobalt-protoporphyrin, a synthetic heme analogue, feminizes hepatic androgen metabolism in the rat.
A single injection of cobalt-protoporphyrin (50 mumol/kg) produced marked changes in the metabolism of 14C-labeled testosterone and 4-androstenedione by male rat liver microsomes and this effect was maintained for at least 3 weeks. The rate of 3 beta- and 5 alpha-reduction was increased to levels observed in untreated adult female animals and cobalt-protoporphyrin altered the metabolic profile of testosterone towards that observed after infusion of growth hormone whereas hypophysectomy produced a more general inhibition of androgen metabolism. The reduction of testosterone or 4-androstenedione by liver microsomes was also increased when cobalt-protoporphyrin (10-30 microM) was added in vitro but a higher concentration (100 microM) led to inhibition of androgen metabolism. The identity of the main androgen metabolites was established by TLC, HPLC and mass spectrometry and the role of 5 alpha-reductase was demonstrated using a specific inhibitor of this enzyme. The possible sites of action of cobalt-protoporphyrin are discussed in relation to its in vivo effects on serum testosterone and LH concentrations.
Galbraith
R A
RA
Rockefeller University Hospital, York Avenue, New York, NY 10021.
Jellinck
P H
PH
D058891:5-alpha Reductase Inhibitors; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D007016:Hypophysectomy; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D000728:Androgens; D001378:Azasteroids; D011166:Porphyrins; D011524:Protoporphyrins; D011725:Pyridines; D013196:Dihydrotestosterone; C013109:metapyrone; D013739:Testosterone; D000735:Androstenedione; D009249:NADP; C007095:cobaltiprotoporphyrin; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D013006:Growth Hormone