Mouse GnRH Receptor Gene Expression Is Mediated by the LHX3 Homeodomain Protein

Appropriate expression of GnRH receptor (GnRHR) is necessary for the correct regulation of the gonadotropins, LH and FSH, by 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, αT3-1, 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.