7alpha-hydroxytestosterone affects 1 beta-hydroxysteroid dehydrogenase 1 direction in rat Leydig cells.
The cytochrome P450 2A1 (CYP2A1) is a P450 enzyme that catalyzes the metabolism of testosterone. CYP2A1 has been reported to be present in rat testis. However, its developmental changes and function have not been well characterized. The purpose of this study was to measure the abundance of CYP2A1 (Cyp2a1) mRNA in the developing rat testis and Leydig cells and examine the effects of its product, 7 alpha-hydroxytestosterone (7HT), on an important enzyme, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) that interconverts active corticosterone and inactive 11-dehydrocorticosterone. As detected by real-time PCR, Cyp2a1 was found to be present exclusively in the Leydig cell. CYP2A1 activity in adult Leydig cells was 5-fold higher than those in progenitor or immature Leydig cells. 7HT competitively suppressed 11 beta-HSD1 oxidase and reductase activities in rat testis microsome with inhibitory constant of 1.2 and 2.9 mum, respectively. In intact Leydig cells, 7HT did not inhibit 11 beta-HSD1 reductase activity, but it stimulated its reductase activity. Thus, at 100 nm and higher concentrations, 7HT significantly switched 11 beta-HSD1 oxidoreductase activities toward reductase. The present data shows that 7HT, the product formed by CYP2A1 from testosterone, regulates the direction of 11 beta-HSD1 activity in rat Leydig cells.
Hu
Guo-Xin
GX
Population Council, 1230 York Avenue, New York, New York 10065, USA.
Lian
Qing-Quan
QQ
Chen
Bing-Bing
BB
Prasad
Pramod V
PV
Kumar
Narender
N
Zheng
Zhi-Qiang
ZQ
Ge
Ren-Shan
RS
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002469:Cell Separation; D000072467:Cytochrome P450 Family 2; D006915:Hydroxytestosterones / Q000494:pharmacology*; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D008297:Male; D009249:NADP / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012038:Regeneration; D013250:Steroid Hydroxylases / Q000235:genetics*; D013737:Testis / Q000201:enzymology / Q000254:growth & development
D006915:Hydroxytestosterones; D012333:RNA, Messenger; C032278:4,17 beta-dihydroxy-4-androstene-3-one; D009249:NADP; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C456179:Cyp2a1 protein, rat; D000072467:Cytochrome P450 Family 2