REGULATION BY GONADOTROPINS OF THE MESSENGER-RIBONUCLEIC-ACID FOR P450 SIDE-CHAIN CLEAVAGE, P450(17-ALPHA)-HYDROXYLASE C-17,C-20-LYASE, AND3-BETA-HYDROXYSTEROID DEHYDROGENASE IN CULTURED PIG LEYDIG-CELLS/

The Leydig cell from the immature pig provides a good model for studyi ng testicular steroidogenesis. Regulation of the enzymes involved, whi ch has been well studied in rodents, has not been characterized in the pig. The objectives of this study were to examine the regulation of t hree steroidogenic enzymes in pig Leydig cells by LH/hCG and testoster one. The mRNA for P450 side-chain cleavage and P450(17 alpha)-hydroxyl ase/C-17-20-lyase, although constitutively expressed, decreased over t ime in culture, while that for 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) remained relatively constant. The mRNA for all three enzymes was increased in a dose- and time-dependent manner by treatment with hCG. Run-on experiments demonstrated that the main effect of the hormo ne was at the level of transcription. Treatment with hydroxyflutamide, either alone or in combination with hCG, had no effect on the mRNA fo r these enzymes. Treatment with hCG plus aminoglutethimide, an inhibit or of steroidogenesis, had no effect on the mRNA for the two P450 enzy mes, but resulted in an increase in mRNA for 3 beta HSD when compared to treatment with hCG alone, However, exogenous testosterone could not block the effect of aminoglutethimide. Therefore, the steroidal regul ation of 3 beta HSD in pig Leydig cells may act through a mechanism se parate from the androgen receptor. While aspects of the regulation of these enzymes are similar to those seen in rodents, some significant d ifferences exist. Our results support the concept that regulation of s teroidogenic enzymes in Leydig cells is species-specific.