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Retinoid-Sensitive Steps in Steroidogenesis in Fetal and Neonatal Rat Testes: In Vitro and In Vivo Studies

INSERM U566-CEA-UNIVERSITE PARIS 7,³ CEA/DSV/DRR BP6, 92265 Fontenay aux Roses, France INSERM U356,⁴ Centre de Recherche Biomédical des Cordeliers, 75270 Paris, France INSERM U369 and IFR d'Endocrinologie,⁵ Faculté de Médecine Lyon-RTH Laennec, 69322 Lyon, France

Retinoic acid (RA) was recently shown to modify testosterone secretion of the fetal testis in vitro. We characterized this effect by culturing rat testes explanted at various ages, from Fetal Day 14.5 to Postnatal Day 3. In basal medium, RA inhibited, in a dose-dependent manner, both basal and acute LH-stimulated testosterone secretion by testes explanted on Fetal Days 14.5, 15.5, and 16.5. It had no effect on testes from older animals. The negative effect of RA did not result from a diminution in the number of Leydig cells but from a decrease in P450c17 mRNA levels and in LH-stimulated cAMP production. However, the RA-induced decrease in P450C17 mRNA levels was also observed with neonatal testes, suggesting that this enzymatic step is no longer rate limiting at this developmental stage. To study the physiological relevance of RA effects, we used fetuses and neonates issued from mothers fed a vitamin A-deficient (VAD) diet, resulting in a threefold decrease of plasma retinol concentration. On Fetal Day 18.5 and on Posnatal Day 3, testosterone secretion by the testis ex vivo was significantly increased in VAD animals. This shows that the endogenous retinol inhibits differentiation and/or function of fetal Leydig cells before Fetal Day 18.5 and is required for the normal regression of fetal Leydig cell function that occurs after Fetal Day 18.5. In conclusion, our results show that retinoids play a negative role on the steroidogenic activity during the differentiation of rat fetal Leydig cells.

¹ Correspondence: René Habert, Gametogenesis and Genotoxicity Unit, INSERM U 566 CEA-Université Paris 7, CEA/DSV/DRR. BP 6. Route du Panorama, Fontenay aux Roses 92265, France. FAX: 33 1 46 54 99 06; rene.habert{at}cea.fr

² Deceased

This article has been cited by other articles:

				R. Lambrot, H. Coffigny, C. Pairault, A.-C. Donnadieu, R. Frydman, R. Habert, and V. Rouiller-Fabre Use of Organ Culture to Study the Human Fetal Testis Development: Effect of Retinoic Acid J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2696 - 2703. [Abstract] [Full Text] [PDF]