This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Google Scholar Articles by Sinkevicius, K. W. Articles by Greene, G. L. PubMed PubMed Citation Articles by Sinkevicius, K. W. Articles by Greene, G. L. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB TESTOSTERONE

Estrogen-Dependent and -Independent Estrogen Receptor- Signaling Separately Regulate Male Fertility

The Ben May Department for Cancer Research (K.W.S., M.L., K.W., G.L.G.), The University of Chicago, Chicago, Illinois 60637; Department of Pathology (T.L.L.), Johns Hopkins Medical Institutions, Baltimore, Maryland 21231; and Division of Pharmacology and Toxicology (J.H.R.), The University of Texas at Austin, Austin, Texas 78712

Address all correspondence and requests for reprints to: Geoffrey Greene, The University of Chicago, 929 East 57th Street, GCIS W330, Chicago, Illinois 60637. E-mail: ggreene{at}uchicago.edu.

Estrogen receptor- (ER) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ER mechanisms are involved in male fertility, we examined male estrogen nonresponsive ER knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ER that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ER pathways. Surprisingly, we found that ligand-independent ER signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ER signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ER knock-in (ENERKI) mice with the ER selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ER in vivo, we discovered male fertility required neonatal estrogen-mediated ER 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 ER in human infertility should be examined more closely.

This article has been cited by other articles:

				A. Khattri, R.K. Pandey, N.J. Gupta, B. Chakravarty, M. Deenadayal, L. Singh, and K. Thangaraj Estrogen receptor {beta} gene mutations in Indian infertile men Mol. Hum. Reprod., August 1, 2009; 15(8): 513 - 520. [Abstract] [Full Text] [PDF]