Inhibition of 17 beta-hydroxysteroid-oxidoreductase activity in purified rat Leydig cells by single injection of human choriogonadotrophin.
A marked decrease of progesterone conversion to androgens in vitro by purified rat testis Leydig cells is observed from 1/2 to 3 days after treatment of the rats with 100 IU human choriogonadotrophin (hCG) in vivo. The maximal inhibition results 2 days after hCG injection and is denoted by a 72% reduction of androstenedione formation and a 78% reduction of testosterone formation from 2.5 mumol progesterone X 1(-1). The testosterone/androstenedione ratio (about 0.4), however, is not changed after hCG treatment, indicating that the 17-ketosteroid-reductase activity is not rate-limiting under these conditions. Nevertheless, testosterone formation from 2.5 mumol androstenedione X 1(-1) is reduced by 67% and androstenedione formation from 2.5 mumol testosterone X 1(-1) is reduced by 79% 1 and 2 days after hCG treatment. The time-course of this hCG-induced decrease in both reductase and oxidase activities of the Leydig cell 17 beta-hydroxysteroid-oxidoreductase parallels the decrease of androgen formation from progesterone Kinetic analyses reveal that the Vmax of the oxidase is reduced to a significantly (P less than 0.05) greater extent than the Vmax of the reductase (79 and 62%, respectively), whereas the respective Km values remain unchanged. From these results it may be concluded that either a loss, or an inactivation of the enzyme protein, or the formation of non-competitive inhibitor occur during hCG action and that hCG may affect different enzyme activities involved in testicular androgen biosynthesis in a similar way.
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D006801:Humans; D007985:Leydig Cells / Q000201:enzymology*; D008297:Male; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism
D006063:Chorionic Gonadotropin; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D015067:17-Hydroxysteroid Dehydrogenases; C032690:3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+))