Follicle-stimulating hormone inhibits all-trans-retinoic acid-induced retinoic acid receptor alpha nuclear localization and transcriptional activation in mouse Sertoli cell lines

The regulation of retinoic acid receptor alpha (RAR alpha) signal transduct ion has not been well characterized. In this study, we determined whether a ll-trans-retinoic acid (tRA) and follicle-stimulating hormone (FSH) modulat e RAR alpha receptor subcellular localization, leading to changes in its tr anscriptional activity and protein expression in mouse Sertoli cell lines. We found that tRA induced the nuclear localization of RARa within 30 min an d that longer term exposure increased the receptor transcriptional activity and RAR alpha protein expression. Conversely, FSH suppressed the tRA-induc ed nuclear localization, transcriptional transactivation, and protein expre ssion of RAR alpha, Treatment with two different protein kinase A-selective antagonists reversed the inhibitory actions of FSH on tRA-dependent RAR al pha nuclear localization and transcriptional activity. These results:are co nsistent with the involvement of protein kinase A in mediating the inhibito ry effects of FSH, For the first time, we demonstrate a unique signaling co ni vergence between the RAR alpha and the FSH-mediated signaling pathways, which may have significant implications in the testis because both are crit ical regulators of testis : physiology.