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This version published online on October 18, 2007
Endocrinology, doi:10.1210/en.2007-1084
A more recent version of this article appeared on January 1, 2008
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*CHORIONIC GONADOTROPIN
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Submitted on August 6, 2007
Accepted on October 10, 2007

Pituitary gonadotroph estrogen receptor alpha (ER{alpha}) is necessary for fertility in females

Mary C. Gieske, Hyun Joon Kim, Sandra J. Legan, Yongbum Koo, Andree Krust, Pierre Chambon, and CheMyong Ko*

Center of Excellence in Reproductive Sciences, University of Kentucky, Lexington, KY 40536; Department of Biology, University of Kentucky, Lexington, KY 40536; Department of Anatomy and Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Korea; Department of Physiology, University of Kentucky, Lexington, KY 40536; School of Biotechnology and Biomedical Sciences, Inje University, Kimhae, South Korea; Institut de Genetique et de Biologie Moleculaire et Cellulaire (CNRS, INSERM, ULP, College de France); Institut Clinique de la Souris, BP 10142, 67404 Illkirch-Strasbourg, France

* To whom correspondence should be addressed. 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 alpha (ER{alpha}) mediates estrogen action in the pituitary gonadotroph. To test this hypothesis, we generated a mouse line with a selective ER{alpha} deletion in the gonadotropin {alpha} subunit ({alpha}GSU)-expressing pituitary cells (pituitary-specific ER{alpha} knockout; ER{alpha}flox/flox {alpha}GSUcre). While the ER{alpha}flox/flox {alpha}GSUcre female mice maintain a basal level of serum luteinizing hormone (LH) and follicle stimulating hormone (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{alpha}flox/flox {alpha}GSUcre female mice express equivalent levels of LH{beta} and {alpha}GSU mRNA compared to wild type mice as determined by microarray analysis. Taken together, these findings indicate that pituitary gonadotroph ER{alpha} carries out the effects of estrogens with regard to estrous cyclicity and ultimately fertility.




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C. Glidewell-Kenney, J. Weiss, L. A. Hurley, J. E. Levine, and J. L. Jameson
Estrogen Receptor {alpha} Signaling Pathways Differentially Regulate Gonadotropin Subunit Gene Expression and Serum Follicle-Stimulating Hormone in the Female Mouse
Endocrinology, August 1, 2008; 149(8): 4168 - 4176.
[Abstract] [Full Text] [PDF]


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