Regulation of Expression of 5 Alpha-Reductase Type 1 in Mouse Leydig Cells

Testosterone is the principal androgen produced in the testis of most species. The enzyme 5a-reductase converts circulating testosterone to dihydrotestosterone in target tissues, a process that is necessary for development of the male phenotype in human beings. However, in some animals, androstanediol, a 5a-reduced androgen, is the primary androgen produced by the testis during certain stages of development, indicating the presence of 5a-reductase in the testis itself. Studies in mice show that while both isozymes of 5a-reductase are absent in the fetal and adult testis, 5a-reductase type 1 is the only form present in the immature (prepubertal) testicular Leydig cells when androstanediol is their principal product. The high testosterone production by the fetal and adult mouse testis is driven by human chorionic gonadotropin and luteinizing hormone, respectively, which act through elevation of intracellular cyclic AMP. Consequently, we hypothesized that 5a-reductase type 1 is constitutively present in the mouse Leydig cell and repressed by cyclic AMP. We screened two mouse Leydig cell lines: MLTC-1 cells&MA-10 cells, for 5a-reductase type 1 activity. Both cell lines expressed abundant 5a-reductase type 1 activity under basal conditions and mmetabolized progesterone to allopregnanolone, but MA-10 cells yielded additional products. Treatment of MLTC-1 cells with forskolin or human chorionic gonadotropin dramatically decreased 5a-reductase type 1 activity in the cells after 1 hour. Future experiments will address the mechanism of this effect, including the changes in transcription, translation, and degradation

Author dc:creator

• Krishnan, Shruti

Contributors dc:contributor

• Auchus, Richard J.

• Androstenediol
• Dihydrotestosterone
• Testosterone

Language dc:language

en

Identifier

61515589

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/755