Endogenous estrogens inhibit mouse fetal Leydig cell development via estrogen receptor alpha.
It is now accepted that estrogens play a role in male fertility and that exposure to exogenous estrogens during fetal/neonatal life can lead to reproductive disorders in the male. However, the estrogen receptor (ER)-mediated processes involved in the regulation of male reproduction during fetal and neonatal development are still largely unclear. We previously reported that ER beta deficiency affects gametogenesis in mice but changes neither the number nor the differentiated functions of fetal Leydig cells. We show here that ER alpha-deficient mice (ER alpha-/-) display higher levels of testicular testosterone secretion than wild-type mice from fetal d 13.5 onwards. This results from higher levels of steroidogenic activity per fetal Leydig cell, as indicated by the hypertrophy of these cells and the higher levels of mRNA for StAR, P450c17 and P450scc in the testis, for a similar number of Leydig cells. Because LH is not produced on fetal d 13.5 and because no change in plasma LH concentration was observed in 2-d-old ER alpha-deficient mice, LH is probably not involved in the effects of estrogens on testicular steroidogenesis in fetal and early neonatal Leydig cells. Furthermore, inactivation of ER beta did not change the effect of ER alpha inactivation on steroidogenesis. Lastly, in an organ culture system, 1 mum diethylstilbestrol decreased the testosterone secretion of wild-type fetal and neonatal testes but not of ER alpha-/- testes. Thus, this study shows that endogenous estrogens physiologically inhibit steroidogenesis via ER alpha by acting directly on the testis early in fetal and neonatal development.
Delbès
Géraldine
G
Unité de Gamétogenèse et Génotoxicité, Institut National de la Santé et de la Recherche Médicale Unité 566, Commissariat à l'Energie Atomique, Université Paris 7, Denis Diderot, Fontenay-aux-Roses, France.
Levacher
Christine
C
Duquenne
Clotilde
C
Racine
Chrystèle
C
Pakarinen
Pirjo
P
Habert
René
R
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D004054:Diethylstilbestrol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000502:physiology*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000166:cytology*; D007985:Leydig Cells / Q000737:chemistry / Q000502:physiology*; D007986:Luteinizing Hormone / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010750:Phosphoproteins / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013737:Testis / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
D047628:Estrogen Receptor alpha; D004967:Estrogens; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D004054:Diethylstilbestrol; D007986:Luteinizing Hormone; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme