REGULATION OF GONADOTROPIN-RELEASING-HORMONE GENE-EXPRESSION IN-VIVO AND IN-VITRO

The pulsatile release of gonadotropin-releasing hormone (GnRH) into th e portal vasculature is responsible for the maintenance of reproductiv e function. Levels of GnRH decapeptide available for this process can be regulated at transcriptional, posttranscriptional, and posttranslat ional levels. In the immortalized neuronal GT1 cell lines which synthe size and secrete GnRH, regulation of GnRH biosynthesis has been studie d using activators of the protein kinase A (PKA), protein kinase C (PK C), and calcium second messenger systems. These substances, while stim ulating GnRH release, cause a universal sal inhibition of all biosynth etic 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 regulat ion of GnRH gene expression appears to be primarily posttranscriptiona l, since changes in GnRH mRNA levels often occur in the absence of cha nges in GnRH primary transcript levels, an index of GnRH gene transcri ption. For example, GnRH mRNA levels increase in response to stimulati on with glutamate analogs, while GnRH primary transcript levels are un changed. However, parallel changes in GnRH mRNA and primary transcript have been observed on proestrus prior to the LH/GnRH surge, suggestin g that the regulation of GnRH mRNA levels in vivo involves a complex i nterplay of transcriptional and posttranscriptional processes. (C) 199 7 Academic Press.