@article {Nagata559, author = {K Nagata and D J Liberato and J R Gillette and H A Sasame}, title = {An unusual metabolite of testosterone. 17 beta-Hydroxy-4,6-androstadiene-3-one.}, volume = {14}, number = {5}, pages = {559--565}, year = {1986}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, 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 chromatography/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.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/14/5/559}, eprint = {https://dmd.aspetjournals.org/content/14/5/559.full.pdf}, journal = {Drug Metabolism and Disposition} }