Synthesis of gonadotrophins and its regulation in the pituitary gland

Regulation of the synthesis of pituitary gonadotrophins LH andFSH has been studied in the rat using either cell-free translationof pituitary mRNAs, or hybridization techniques with syntheticoligodeoxynucleotides or cloned complementary DNAs. Gonadectomygreatly increases and supplementing gonadectomized rats withgonadal steroids diminishes the rate of synthesis of the gonadotrophinsubunits. Hybridization experiments suggest that gonadal steroidsregulate the expression of the genes coding for pituitary gonadotrophinsubunit precursors. Using the incorporation of labelled methionineby pituitary cells in culture, followed by specific immunoprecipitationof LH-related subunits and SDS-poly-acrylamide gel analysisof immunoprecipitated peptides, there was evidence that gonadotrophinreleasing hormone (GnRH) significantly enhances the radioactivityincorporated into both - and LH-subunits. This effect is specific,it is not a secondary effect due to the release of LH. A cyclicAMP (cAMP) analogue, 8-Br-cAMP, as well as forskolin and choleragen,which are cAMP generators and a diacylglycerol analogue, tetradecanoylphorbolacetate (TPA), mimic the stimulatory action of GnRH on the synthesisof the polypeptide chains of LH. However, no evidence has beenobtained that either cAMP or diacylglycerols mediate this GnRHeffect. These results suggest that the synthesis of pituitarygonadotrophins is under a double control of gonadal steroidsand GnRH which exert opposite effects, inhibitory for steroidsand stimulatory for GnRH. The negative control by steroids occursat the genomic level, while the positive effect of GnRH proceedsvia different mechanisms which remain to be elucidated.