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Author Sinkevicius, Kerstin W. ♦ Laine, Muriel ♦ Lotan, Tamara L. ♦ Woloszyn, Karolina ♦ Richburg, John H. ♦ Greene, Geoffrey L.
Source Paperity
Content type Text
Publisher Oxford University Press
File Format PDF ♦ HTM / HTML
Copyright Year ©2009
Abstract Estrogen receptor-α (ERα) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERα mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERα knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERα that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ERα pathways. Surprisingly, we found that ligand-independent ERα signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ERα signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ERα knock-in (ENERKI) mice with the ERα selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ERα in vivo, we discovered male fertility required neonatal estrogen-mediated ERα 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 ERα in human infertility should be examined more closely.
Learning Resource Type Article
Publisher Date 2009-06-01
Journal Endocrinology
Volume Number 150
Issue Number 6