Inhibition of 17β-hydroxysteroid-oxidoreductase activity in purified rat Leydig cells by single injection of human choriogonadotrophin

Abstract

Abstract. 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 μmol progesterone · l7#x2212;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 μmol androstenedione · l−1 is reduced by 67% and androstenedione formation from 2.5 μmol testosterone · l−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 17β-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 < 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.