Testosterone Decreases 3 Beta-hydroxysteroid Dehydrogenase-isomerase Messenger Ribonucleic Acid In Cultured Mouse Leydig Cells By A Strain-specific Mechanism
Creator
Heggland S J; Signs S A; Stalvey J R D
Publisher
Journal of Andrology
Date
1997
1997-11
Description
We previously reported a strain-related difference in basal 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta HSD) activity in response to testosterone in cultured Leydig cells. The data suggested that the response to testosterone was androgen receptor mediated and that testosterone was acting via a irans-acting factor distal to the androgen receptor to regulate Leydig cell basal 3 beta HSD activity. This study was designed to determine whether the previous reported strain-related difference in basal 3 beta HSD activity in response to testosterone was due to a difference at the 3 beta HSD protein and/or at the mRNA level, In C57BL/6J Leydig cells, 2.0 mu M testosterone significantly decreased basal 3 beta HSD immunoreactive mass by day 6 in culture. Treatment with 2.0 mu M testosterone and 2.0 mu M hydroxyflutamide, an androgen receptor antagonist, negated the inhibitory effect of testosterone on C57BL/6J 3 beta HSD immunoreactive mass, Treatment with 2.0 mu M testosterone also significantly decreased 3 beta HSD mRNA content in C57BL/6J Leydig cells, which was detectable on day 3 in culture, In contrast to Leydig cells from C57BL/6J mice, Leydig cells from C3H/HeJ mice were not susceptible to the inhibitory effect of testosterone on 3 beta HSD. Treatment with 2.0 mu M testosterone had no detectable effect on C3H/HeJ 3 beta HSD immunoreactive mass or mRNA content at any time point in culture. These data indicate that the testosterone-induced loss of basal 3 beta HSD activity in C57BL/6J Leydig cells can he accounted for by the lass of 3 beta HSD immunoreactive mass, which is preceded by the loss of 3 beta HSD mRNA, and that the strain-related difference in the regulation of 3 beta HSD is present at all three levels. Thus, the putative trans-acting factor involved in the mechanism whereby testosterone decreases basal 3 beta HSD is likely to regulate the amount of 3 beta HSD mRNA.