| First Author | Sinkevicius KW | Year | 2009 |
| Journal | Endocrinology | Volume | 150 |
| Issue | 6 | Pages | 2898-905 |
| PubMed ID | 19264877 | Mgi Jnum | J:158183 |
| Mgi Id | MGI:4438183 | Doi | 10.1210/en.2008-1016 |
| Citation | Sinkevicius KW, et al. (2009) Estrogen-dependent and -independent estrogen receptor-alpha signaling separately regulate male fertility. Endocrinology 150(6):2898-905 |
| abstractText | Estrogen receptor-alpha (ERalpha) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERalpha mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERalpha knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERalpha that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ERalpha pathways. Surprisingly, we found that ligand-independent ERalpha signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ERalpha signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ERalpha knock-in (ENERKI) mice with the ERalpha selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ERalpha in vivo, we discovered male fertility required neonatal estrogen-mediated ERalpha signaling. Thus, our work indicates both estrogen-dependent and -independent pathways play separable roles in male murine reproductive tract development and that the role of ERalpha in human infertility should be examined more closely. |
