| Popis: |
Summary In this review we have assembled the recent literature concerning the molecular aspects of GnRH gene regulation. Since investigation of the molecular mechanisms of gene expression requires an appropriate cell model system, we have focused on experiments performed in the GT1 hypothalamic neuronal cell line. Important regions of the GnRH gene, including a neuron-specific enhancer region and a proximal promoter, have been determined and proteins that bind to these regions are now being identified. Thus far, GATA transcription factors and the Oct-1 transcription factor are known to bind the GnRH gene. Several other proteins have been detected but their identities are still unknown. Understanding how these proteins are involved in a neuron-specific enhancer will increase both our knowledge of GnRH regulation and the mechanisms underlying tissue specificity in general. Some of these proteins may be targets of the PKC and cGMP-dependent protein kinase signal transduction pathways known to effect GnRH transcription. Thus far agents that affect these pathways have been found to induce secretion of GnRH in the short term, but cause downregulation of the GnRH gene in the long term. It is hoped that by understanding the molecular mechanisms underlying GnRH synthesis, rational treatments for endocrine and reproductive diseases involving GnRH will result. |
