title: Intestinal and hepatic microsomal metabolism of testosterone and progesterone by a 3 alpha-hydroxysteroid dehydrogenase to the 3 alpha-hydroxy derivatives in the channel catfish, Ictalurus punctatus.
abstract: Intestinal or hepatic microsomes from channel catfish converted [4-14C]-testosterone to three major metabolites: 6 beta-hydroxytestosterone, androstenedione and a third metabolite. Formation of the unknown metabolite required NADPH as cofactor. When incubated with 200 microM testosterone, the rate of formation of the unknown metabolite was 265+/-158 pmol/(min mg) protein (mean+/-S.D.) in microsomes from the proximal intestine, 515+/-93 pmol/(min mg) protein in distal intestine and 226+/-42 pmol/(min mg) protein in hepatic microsomes. Comparison of the chromatographic and spectral properties of the unknown metabolite with those of authentic testosterone derivatives showed that this metabolite corresponded to 4-androstene-3 alpha,17 beta-diol. No 3 alpha-reduced metabolite was formed in incubations of testosterone with catfish intestinal cytosol. Testosterone was reduced to 5 alpha-dihydrotestosterone primarily in the cytosolic fraction and not in microsomes. Incubation of progesterone with intestinal microsomes resulted in the formation of a metabolite with properties similar to that of the 3 alpha-reduced testosterone, and this metabolite was identified by co-chromatography with authentic standard as 3 alpha-reduced progesterone. Thus, 3 alpha-hydroxysteroid dehydrogenase is an important pathway in intestinal microsomes of the channel catfish.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, P.O. Box 100485, Gainesville 32610-0485, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lou
authors.forename: Jodie V
authors.initials: JV
authors.lastname: Johnson
authors.forename: Margaret O
authors.initials: MO
authors.lastname: James
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003600:Cytosol; D013196:Dihydrotestosterone / Q000378:metabolism; D006915:Hydroxytestosterones / Q000378:metabolism; D007059:Ictaluridae; D007413:Intestinal Mucosa / Q000378:metabolism*; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
chemical_list: D006915:Hydroxytestosterones; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D009249:NADP; C025591:6 beta-hydroxytestosterone; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)