Transcriptional regulation of the GnRH receptor gene by glucocorticoids

Abstract

Expression of the gonadotropin-releasing hormone (GnRH) receptor gene is stimulated by dexamethasone in GnRH-deficient rodents. In this study we identify a 1226 bp sequence at the 5′-flanking region of the mouse GnRH-R gene that confers dexamethasone responsiveness when expressed in host cells. Further, a glucocorticoid antagonist blocks transcriptional activity of the mGnRHR promoter. Progressive 5′-deletion of the mGnRHR promoter localized the response sequence between the −331/−255 region. Analysis of this region revealed binding sites for the AP-1 transcription factor. Mutation in AP-1 modified the functional activity of the mGnRHR promoter following GnRH agonist or dexamethasone-stimulation. Using an electrophoretic mobility shift assay, a protein complex is shown to bind to the AP-1 site. These results suggest that AP-1 proteins and glucocorticoid receptor regulate transcription of the GnRH-R promoter in a heterologous system.