Transcriptional regulation of the gonadotropin-releasing hormone receptor gene is mediated in part by a putative repressor element and by the cyclic adenosine 3 ',5 '-monophosphate response element

The levels of the GnRH receptor (GnRHR) and its messenger RNA depend on the pattern of administration of GnRH. In this study, internal deletion mutant s in a luciferase reporter gene vector (GnRHR-pXP2) containing a 1226-bp pr omoter fragment of mouse GnRHR gene were used to examine the regulation of GnRHR gene transcription in GGH(3) cells. Our results indicate that the mou se GnRHR promoter contains one putative repressor element located at positi on -343/-335. When this sequence was deleted, the GnRHR promoter activity w as significantly increased in both basal and GnRH agonist (Buserelin)-, pho rbol ester-, and forskolin-stimulated cells. Gel mobility shift assay showe d that the sequence -343/-335 is capable of binding GGH(3) nuclear proteins . With deletion of the cAMP response element (-107/-100), basal and Buserel in-stimulated transcription was decreased. The same response was observed a fter stimulation with forskolin. Stimulation with (Bu)(2)cAMP did not alter transcription above basal levels. The stimulation with phorbol ester resul ted in an attenuated increase in transcriptional activity, suggesting that this sequence of the GnRHR promoter is a cAMP response element. These resul ts suggest that the transcriptional activity of the GnRHR gene is mediated in part by a putative repressor element and by the cAMP response element.