Synthesis of gonadotrophins and its regulation in the pituitary gland

Regulation of the synthesis of pituitary gonadotrophins LH and FSH has been studied in the rat using either cell-free translation of pituitary mRNAs, or hybridization techniques with synthetic oligodeoxynucleotides or cloned complementary DNAs. Gonadectomy greatly increases and supplementing gonadectomized rats with gonadal steroids diminishes the rate of synthesis of the gonadotrophin subunits. Hybridization experiments suggest that gonadal steroids regulate the expression of the genes coding for pituitary gonadotrophin subunit precursors. Using the incorporation of labelled methionine by pituitary cells in culture, followed by specific immunoprecipitation of LH-related subunits and SDS-polyacrylamide gel analysis of immunoprecipitated peptides, there was evidence that gonadotrophin releasing hormone (GnRH) significantly enhances the radioactivity incorporated into both alpha- and LH beta-subunits. This effect is specific, it is not a secondary effect due to the release of LH. A cyclic AMP (cAMP) analogue, 8-Br-cAMP, as well as forskolin and choleragen, which are cAMP generators and a diacylglycerol analogue, tetradecanoylphorbol acetate (TPA), mimic the stimulatory action of GnRH on the synthesis of the polypeptide chains of LH. However, no evidence has been obtained that either cAMP or diacylglycerols mediate this GnRH effect. These results suggest that the synthesis of pituitary gonadotrophins is under a double control of gonadal steroids and GnRH which exert opposite effects, inhibitory for steroids and stimulatory for GnRH. The negative control by steroids occurs at the genomic level, while the positive effect of GnRH proceeds via different mechanisms which remain to be elucidated.