Steroid 5 alpha-reductase activity in endothelial cells from human umbilical cord vessels.
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.
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*
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(+))