title: Steroid 5 alpha-reductase activity in endothelial cells from human umbilical cord vessels.
abstract: The metabolism of radiolabeled progesterone and androstenedione was evaluated in endothelial cells from human umbilical cord vein and arteries maintained in culture. The predominant metabolite of progesterone was 5 alpha-pregnane-3,20-dione and that of androstenedione was 5 alpha-androstane-3,17-dione. Thus, the major pathway of progesterone and androstenedione metabolism within these cells is via steroid 5 alpha-reductase. The rate of formation of 5 alpha-pregnane-3,20-dione from progesterone by venous endothelial cells was linear with incubation time up to 4 h and with cell number up to 1.6 X 10(6) cells/ml. The apparent Km of 5 alpha-reductase for progesterone was 0.4 microM; and, the Vmax was 55 pmol 5 alpha-pregnane-3,20-dione formed/mg protein X h. The rate of 5 alpha-androstane-3,17-dione formation from androstenedione also was linear with incubation time up to 4 h. In addition to 5 alpha-androstane-3,17-dione, the metabolism of androstenedione by either venous or arterial cells resulted in the formation of various minor metabolites, including testosterone and 5 alpha-reduced steroids, viz. 5 alpha-dihydrotestosterone, androsterone, isoandrosterone, 5 alpha-androstane-3 alpha, 17 beta-diol, and 5 alpha-androstane-3 beta, 17 beta-diol. Estrogens (i.e. estradiol-17 beta and estrone) were not detected as products of androstenedione metabolism. The formation of these metabolites are indicative that the steroid-metabolizing enzymes present in endothelial cells are: 5 alpha-reductase, 17 beta-hydroxysteroid oxidoreductase, 3 alpha-hydroxysteroid oxidoreductase, and 3 beta-hydroxysteroid oxidoreductase.
mesh_terms: D043582:5-alpha-Dihydroprogesterone; D000728:Androgens / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D002478:Cells, Cultured; D004727:Endothelium / Q000201:enzymology*; D004967:Estrogens / Q000378:metabolism; D007700:Kinetics; D010088:Oxidoreductases / Q000378:metabolism*; D011277:Pregnanediones / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D014469:Umbilical Arteries / Q000201:enzymology*; D014471:Umbilical Veins / Q000201:enzymology*
chemical_list: D000728:Androgens; D004967:Estrogens; D011277:Pregnanediones; D000735:Androstenedione; D011374:Progesterone; D043582:5-alpha-Dihydroprogesterone; D010088:Oxidoreductases; C022447:3-oxo-5-alpha-steroid 4-dehydrogenase (NADP(+))