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 (RARalpha) signal transduction has not been well characterized. In this study, we determined whether all-trans-retinoic acid (tRA) and follicle-stimulating hormone (FSH) modulate RARalpha 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 RARalpha within 30 min and that longer term exposure increased the receptor transcriptional activity and RARalpha protein expression. Conversely, FSH suppressed the tRA-induced nuclear localization, transcriptional transactivation, and protein expression of RARalpha. Treatment with two different protein kinase A-selective antagonists reversed the inhibitory actions of FSH on tRA-dependent RARalpha 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 RARalpha and the FSH-mediated signaling pathways, which may have significant implications in the testis because both are critical regulators of testis physiology.
Braun
K W
KW
School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington 99164, USA.
Tribley
W A
WA
Griswold
M D
MD
Kim
K H
KH
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D011962:Receptors, FSH / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D012708:Sertoli Cells; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
D007546:Isoquinolines; D009687:Nuclear Proteins; C000607072:Rara protein, mouse; D011962:Receptors, FSH; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D013449:Sulfonamides; D014212:Tretinoin; D003994:Bucladesine; D005640:Follicle Stimulating Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide