Sex differences in indomethacin-sensitive 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol.
The 3 alpha-hydroxysteroid:nicotinamide adenine dinucleotide (phosphate) oxidoreductase (EC 1.1.1.50) of rat liver cytosol is indistinguishable from trans-1,2-dihydrobenzene-1,2-diol dehydrogenase (EC 1.3.1.20) (T.M. Penning, I. Mukharji, S. Barrows, and P. Talalay, Biochem. J., 222: 601-611, 1984) and has been implicated in the detoxification of ultimate carcinogens (H. R. Glatt et al., Science (Wash. DC), 215: 1507-1509, 1982). Using trans-1,2-dihydroxy-3,5-cyclohexadiene as a model substrate for trans-dihydrodiol proximate carcinogens, this study shows that the specific activity of 3 alpha-hydroxysteroid:nicotinamide adenine dinucleotide (phosphate) oxidoreductase is 2-fold higher in the 40-75% ammonium sulfate fraction prepared from female rat liver cytosol than in similar fractions prepared from males. Comparable differences were also observed for the nicotinamide adenine dinucleotide-dependent oxidation of 5 alpha-androstan-3 alpha-ol-17-one. Chromatofocusing of these cytosolic fractions separated the bulk of the protein from the dehydrogenase, which eluted as a single peak at pH 5.4. Examination of the protein profiles indicates that twice as much protein coeluted with the enzyme from female rat liver cytosol, suggesting that induction is responsible for the sex difference in enzyme activity. These differences were abolished by ovariectomy, while administration of a single dose of estradiol 3-sulfate (100 micrograms) to ovariectomized rats restored enzyme activity to within 90% of normal female levels. These findings suggest that ovarian estrogen is a natural inducer of rat liver 3 alpha-hydroxysteroid:nicotinamide adenine dinucleotide (phosphate) oxidase reductase/trans-1,2-dihydrobenzene-1,2-diol dehydrogenase.
D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000818:Animals; D002369:Castration; D002845:Chromatography; D003600:Cytosol / Q000201:enzymology*; D004790:Enzyme Induction; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D004967:Estrogens; D008748:Methylcholanthrene; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D007213:Indomethacin