Organization and expression of gonadotropin genes

We have examined the question of how hormones regulate the biosynthesis of gonadotropins. In particular we have studied the effects of gonadal sex steroid hormones on the regulation of LH subunit gene expression to determine whether they may occur at the pre-translational level. Success in the molecular cloning of cDNAs in genes encoding the subunits of LH has allowed such studies. It is now known that the subunit genes are located in separate genes on separate chromosomes in man and mouse. These genes must be coordinately expressed in a tissue-specific fashion in gonadotropes to yield subunit mRNAs which are ultimately translated to form the protein backbones of the subunits. It is clear that the gonadal sex steroid hormones in both castration and castration-replacement experimental paradigms negatively regulate the subunit mRNAs in vivo in a rapid and effective manner. Also, it is interesting to note that alpha-subunit RNA is regulated to a lesser extent than the LH beta. This observation is reminiscent of those previously observed in the studies of the biosynthesis of TSH in which the subunit mRNA is less well controlled than the TSH beta mRNA. These studies were performed initially using thyrotropic tumor which lacked confounding gonadotropes. However, studies have also been performed in the pituitary gland of the hypothyroid mouse with similar results. Hence, it appears that the alpha subunit gene is also under regulation by hormones but to a lesser extent than the LH beta. These findings provide hope that future studies will allow us to understand further the molecular mechanisms involved in the regulation of these genes by various hormonal influences.