title: Product inhibition of steroid-17 alpha-monooxygenase by endogenous 17 alpha-hydroxyprogesterone in microsomes and isolated Leydig cells from rat testis.
abstract: Use of integrated rate equations for analysis of progesterone metabolism by isolated Leydig cells and microsomes from rat testis in presence of several progesterone concentrations within several periods reveals competitive product inhibition by endogenously formed 17 alpha-hydroxyprogesterone (Kpm = 0.1 microM) of steroid-17 alpha-monooxygenase activity (Ksm = 0.8 microM). The discrepancy between this very low interaction constant of endogenous 17 alpha-hydroxyprogesterone with the steroid-17 alpha-monooxygenase, and the respective values (from the literature) for exogenous 17 alpha-hydroxyprogesterone which are about 50-fold higher, may be explained by accumulation of endogenous 17 alpha-hydroxyprogesterone at the catalytic site of the steroid-17 alpha-monooxygenase. This mechanism may be important for intratesticular regulation of androgen biosynthesis from precursor steroids.
mesh_terms: D019326:17-alpha-Hydroxyprogesterone; D000818:Animals; D005246:Feedback; D006908:Hydroxyprogesterones / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D007985:Leydig Cells / Q000201:enzymology; D008297:Male; D008433:Mathematics; D008861:Microsomes / Q000201:enzymology; D008956:Models, Chemical; D051381:Rats; D011919:Rats, Inbred Strains; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013737:Testis / Q000201:enzymology*
chemical_list: D006908:Hydroxyprogesterones; D019326:17-alpha-Hydroxyprogesterone; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase