Transcriptional regulation of the GnRH receptor gene by glucocorticoids.
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.
Maya-Núñez
Guadalupe
G
Oregon National Primate Research Center, Portland 97201, USA.
Conn
P Michael
PM
D000818:Animals; D001483:Base Sequence; D002064:Buserelin / Q000819:agonists; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D016758:Genes, jun; D005822:Genetic Vectors / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011966:Receptors, LHRH / Q000235:genetics*; D017384:Sequence Deletion; D014158:Transcription, Genetic
D005938:Glucocorticoids; D011966:Receptors, LHRH; D003907:Dexamethasone; D002064:Buserelin