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Pituitary Gonadotroph Estrogen Receptor- Is Necessary for Fertility in Females

Center of Excellence in Reproductive Sciences (M.C.G., H.J.K., C.K.) and Departments of Biology (M.C.G., C.K.) and Physiology (S.J.L.), University of Kentucky, Lexington, Kentucky 40536; Department of Anatomy and Neurobiology (H.J.K.), Institute of Health Sciences, School of Medicine, Gyeongsang National University, 660-751 Jinju, Korea; School of Biotechnology and Biomedical Sciences (Y.K.), Inje University, 621-749 Kimhae, South Korea; and Institut de Genetique et de Biologie Moleculaire et Cellulaire (A.K., P.C.) (Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, College de France), Institut Clinique de la Souris, 67404 Illkirch-Strasbourg, France

Address all correspondence and requests for reprints to: CheMyong Ko, Ph.D., Division of Clinical and Reproductive Sciences, University of Kentucky, Lexington, Kentucky 40536. E-mail: cko2{at}uky.edu.

Estrogens play a central role in regulating female reproduction throughout the reproductive axis, and the pituitary is one of the major targets of estrogen action. We hypothesized that estrogen receptor (ER) mediates estrogen action in the pituitary gonadotroph. To test this hypothesis, we generated a mouse line with a selective ER deletion in the gonadotropin -subunit (GSU)-expressing pituitary cells (pituitary-specific ER knockout; ER^flox/flox GSU^cre). Although the ER^flox/flox GSU^cre female mice maintain a basal level of serum LH and FSH and their ovulatory capacity is comparable to that in controls, they do not display regular estrous cycles and are infertile, indicating a potential disorder in regulating LH and/or FSH secretion. The ER^flox/flox GSU^cre female mice express equivalent levels of LHβ and GSU mRNA compared with wild-type mice as determined by microarray analysis. Taken together, these findings indicate that pituitary gonadotroph ER carries out the effects of estrogens with regard to estrous cyclicity and ultimately fertility.

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