Regulation of gonadotropin-releasing hormone gene expression in vivo and in vitro.
The pulsatile release of gonadotropin-releasing hormone (GnRH) into the portal vasculature is responsible for the maintenance of reproductive function. Levels of GnRH decapeptide available for this process can be regulated at transcriptional, posttranscriptional, and posttranslational levels. In the immortalized neuronal GT1 cell lines which synthesize and secrete GnRH, regulation of GnRH biosynthesis has been studied using activators of the protein kinase A (PKA), protein kinase C (PKC), and calcium second messenger systems. These substances, while stimulating GnRH release, cause a universal inhibition of all biosynthetic indices measured to date, including decreases in transcription of the proGnRH gene, GnRH mRNA levels, mRNA stability, and translational efficiency. In contrast, in the animal, the mechanism for the regulation of GnRH gene expression appears to be primarily posttranscriptional, since changes in GnRH mRNA levels often occur in the absence of changes in GnRH primary transcript levels an index of GnRH gene transcription. For example, GnRH mRNA levels increase in response to stimulation with glutamate analogs, while GnRH primary transcript levels are unchanged. However, parallel changes in GnRH mRNA and primary transcript have been observed on proestrus prior to the LH/GnRH surge, suggesting that the regulation of GnRH mRNA levels in vivo involves a complex interplay of transcriptional and posttranscriptional processes.
Gore
A C
AC
Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Roberts
J L
JL
D000818:Animals; D002460:Cell Line; D005091:Exons; D005786:Gene Expression Regulation / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D007438:Introns; D051379:Mice; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D012323:RNA Processing, Post-Transcriptional
D018377:Neurotransmitter Agents; D007987:Gonadotropin-Releasing Hormone