AN UNUSUAL METABOLITE OF TESTOSTERONE - 17 BETA-HYDROXY-4,6-ANDROSTADIENE-3-ONE

  • 1 September 1986
    • journal article
    • research article
    • Vol. 14  (5) , 559-565
Abstract
A testosterone metabolite, 17.beta.-hydroxy-4,6-androstadiene-3-one, possessing an absorbance maximum at 284 nm, was formed during incubation of testosterone with liver microsomes from dexamethasone-treated rats. The metabolite was identified by HPLC, UV spectroscopy, and thermospray liquid chromatograpy/mass spectrometry. The formation of this metabolite by rat liver microsomes required NADPH and oxygen and was inhibited markedly by SKF 525-A, 2,4-dichloro-6-phenylphenoxyethylamine, or CO/O2 (8:2, v/v), but not by cyanide, an inhibitor for stearyl-CoA desaturase. Pretreatment of rats with phenobarbital, pregnenolone 16.alpha.-carbonitrile, and dexamethasone enhanced the formation of this metabolite in parallel with the increase in formation of 6.beta.-hydroxytestosterone (r2 = 0.99). Although 16-methylprogesterone, a known 6.beta.-hydroxylase inhibitor, competitively inhibited the formation of the metabolite and 6.beta.-hydroxytestosterone by liver microsomes from dexamethasone-treated rats, the metabolite was not formed from either 6.beta.-hydroxytestosterone or 7-hydroxytestosterone during incubation with liver microsomes. These findings are consistent with the view that cytochrome P-450 isozymes that catalyze 6.beta.-hydroxylation of steroids in rat liver microsomes also catalyze the dehydrogenation of testosterone to form a double bond between the C-6 and C-7 positions.