title: Homologous upregulation of gonadotropin-releasing hormone receptor mRNA occurs through transcriptional activation rather than modulation of mRNA stability.
abstract: In a previous study, we showed that even continuous application of gonadotropin-releasing hormone (GnRH) could increase the steady-state levels of GnRH receptor (GnRH-R) mRNA if treated for a relatively short period (6 h). Therefore, in the present study we examined whether GnRH-induced increment of GnRH-R mRNA is owing to stabilization of the preexisting GnRH-R mRNA or new synthesis of GnRH-R mRNA or both. Initially, to examine the effect on new RNA synthesis, the transcription inhibitor, actinomycin D (2 microM), was added to primary cultured rat anterior pituitary cells. In the presence of transcription inhibitor, GnRH-induced augmentation of GnRH-R mRNA levels was completely abolished. This result indicates that homologous upregulation of GnRH-R mRNA expression occurs at least through new RNA synthesis of GnRH-R gene. We further assessed the effects of GnRH on the turnover rate of GnRH-R mRNA using actinomycin D (2 microM). The basal half-life of GnRH-R mRNA was estimated to be approx 21 h. The application of GnRH tended to slightly suppress the basal turnover rate of GnRH; however, there was no statistically significant difference, compared with the group treated with actinomycin D alone. Collectively, our results suggest that the homologous upregulation of GnRH-R mRNA may occur through transcriptional activation of GnRH-R gene rather than enhancement of GnRH-R mRNA stability, although we did not examine the transcription rate of GnRH-R gene.
authors.affiliation: Endocrine Laboratory, College of Medicine, Yonsei University, Seoul, South Korea.
authors.forename: M
authors.initials: M
authors.lastname: Cheon
authors.forename: D
authors.initials: D
authors.lastname: Park
authors.forename: Y
authors.initials: Y
authors.lastname: Park
authors.forename: K
authors.initials: K
authors.lastname: Kam
authors.forename: S D
authors.initials: SD
authors.lastname: Park
authors.forename: K
authors.initials: K
authors.lastname: Ryu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004355:Drug Stability; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006207:Half-Life; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011966:Receptors, LHRH / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D011966:Receptors, LHRH; D003609:Dactinomycin; D007987:Gonadotropin-Releasing Hormone