7α-hydroxytestosterone affects 11ß-hydroxysteroid dehydrogenase 1 direction in rat Leydig cells
Hu,Guo-Xin; Lian,Qing-Quan; Chen,Bing-Bing; Vishwanath Prasad,Pramod; Kumar,Narender; Zheng,Zhi-Qiang; Ge,Renshan
Endocrinology 151(2): 748-754
Publication date: 2010
The cytochrome P450 2A1 (CYP2A1) is a P450 enzyme that catalyzesthe metabolism of testosterone. CYP2A1 has been reported tobe present in rat testis. However, its developmental changesand function have not been well characterized. The purpose ofthis study was to measure the abundance of CYP2A1 (Cyp2a1) mRNAin the developing rat testis and Leydig cells and examine theeffects of its product, 7-hydroxytestosterone (7HT), on an importantenzyme, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1)that interconverts active corticosterone and inactive 11-dehydrocorticosterone.As detected by real-time PCR, Cyp2a1 was found to be presentexclusively in the Leydig cell. CYP2A1 activity in adult Leydigcells was 5-fold higher than those in progenitor or immatureLeydig cells. 7HT competitively suppressed 11ß-HSD1 oxidaseand reductase activities in rat testis microsome with inhibitoryconstant of 1.2 and 2.9 µM, respectively. In intact Leydigcells, 7HT did not inhibit 11ß-HSD1 reductase activity,but it stimulated its reductase activity. Thus, at 100 nM andhigher concentrations, 7HT significantly switched 11ß-HSD1oxidoreductase activities toward reductase. The present datashows that 7HT, the product formed by CYP2A1 from testosterone,regulates the direction of 11ß-HSD1 activity in rat Leydigcells.