{"database":"biostudies-other","file_versions":[],"scores":null,"additional":{"submitter":["Sinkevicius KW"],"funding":["NIEHS NIH HHS","NCI NIH HHS"],"pagination":["2898-905"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2689797"],"abstract":["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."],"repository":["biostudies-other"],"data_source":["Europe PMC"],"omics_type":["Unknown"],"volume":["150(6)"],"journal":["Endocrinology"],"pmcid":["PMC2689797"],"funding_grant_id":["R01 ES016591","CA89089"],"pubmed_authors":["Laine M","Lotan TL","Woloszyn K","Richburg JH","Sinkevicius KW","Greene GL"],"additional_accession":[]},"is_claimable":false,"name":"Estrogen-dependent and -independent estrogen receptor-alpha signaling separately regulate male fertility.","description":"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.","dates":{"release":"2009-01-01T00:00:00Z","publication":"2009 Jun","modification":"2019-03-27T00:22:43Z","creation":"2019-03-27T00:22:43Z"},"accession":"S-EPMC2689797","cross_references":{"pubmed":["19264877"],"doi":["10.1210/en.2008-1016 "]}}