Follicle-stimulating Hormone Inhibits All-trans-retinoic Acid-induced Retinoic Acid Receptor α Nuclear Localization and Transcriptional Activation in Mouse Sertoli Cell Lines

The regulation of retinoic acid receptor alpha (RARα) signal transduction has not been well characterized. In this study, we determined whether all-trans-retinoic acid (tRA) and follicle-stimulating hormone (FSH) modulate RARα receptor subcellular localization, leading to changes in its transcriptional activity and protein expression in mouse Sertoli cell lines. We found that tRA induced the nuclear localization of RARα within 30 min and that longer term exposure increased the receptor transcriptional activity and RARα protein expression. Conversely, FSH suppressed the tRA-induced nuclear localization, transcriptional transactivation, and protein expression of RARα. Treatment with two different protein kinase A-selective antagonists reversed the inhibitory actions of FSH on tRA-dependent RARα nuclear localization and transcriptional activity. These results are consistent with the involvement of protein kinase A in mediating the inhibitory effects of FSH. For the first time, we demonstrate a unique signaling convergence between the RARα and the FSH-mediated signaling pathways, which may have significant implications in the testis because both are critical regulators of testis physiology.