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Submitted on December 3, 2004
Accepted on February 1, 2005
Departments of Reproductive Medicine (S.M.M., J.S.B., R.R., B.J.K., P.L.M.) and Neurosciences (P.L.M.), the Biomedical Sciences Graduate Program (S.M.M., J.S.B., P.L.M.) and the Center for Reproductive Science and Medicine (S.M.M., J.S.B., R.R., B.J.K., P.L.M.), University of California San Diego, La Jolla California, 92093-0674
* To whom correspondence should be addressed. E-mail: pmellon{at}ucsd.edu.
Appropriate expression of gonadotropin-releasing hormone receptor (GnRHR) is necessary for the correct regulation of the gonadotropins, LH (LH) and follicle-stimulating hormone (FSH), by gonadotropin-releasing hormone (GnRH). GnRHR is primarily expressed in the gonadotrope cells of the anterior pituitary and a number of regulatory elements important for both basal and hormonal regulation of the gene have been identified. Using the gonadotrope-derived cell line, 
T3-1, that endogenously expresses GnRHR, we have identified an ATTA element located at -298 relative to the transcriptional start site that is essential for basal expression of the GnRHR gene. LHX3, a member of the LIM-homeodomain family, binds the -298 ATTA site in vitro as well as to the endogenous GnRHR promoter in vivo. Additionally, LHX3 specifically activates through this -298 ATTA site in transient transfection assays. LHX3 is essential for pituitary development and has been implicated in the regulation of a number of pituitary specific genes, however, this is the first report identifying its role in the regulation of GnRHR.
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