Signal transduction pathways and transcription factors involved in the gonadotropin-releasing hormone-stimulated gonadotropin subunit gene expression.

Gonadotropin-releasing hormone (GnRH) stimulates gonadotropin (GTH) subunit gene expression via G protein-coupled membrane receptors. GnRH-stimulated GTH subunit gene expression is mediated by protein kinase C (PKC) and Ca(2+) signaling pathways. Recent numerous reports on signal transduction pathways which are involved in GnRH stimulation of mammalian GTH subunit genes showed differential sensitivity of GTH subunit genes to the two signaling pathways. Our recent studies on salmon GTH (sGTH) IIbeta subunit gene showed that its stimulation by GnRH is dependent on the PKC pathway. Furthermore, gel retardation and mutagenesis studies suggested that pituitary homeo box 1 (Ptx1) and Sp1 mediate the GnRH-induced PKC signaling on the sGTHIIbeta gene. However, both PKC and Ca(2+) pathways are involved in the GnRH-stimulated GTH alpha and LHbeta genes. Different preference to the pathways were often reported in a certain GTH subunit gene in different circumstances, suggesting that molecular targets of the two signaling pathways are different. Ets-related factor and cAMP response element binding protein have been proposed as targets of GnRH signaling on GTH alpha genes. Sp1 and early growth response protein 1 play pivotal roles in GnRH-stimulated LHbeta gene expression in synergism with steroidogenic factor-1 and Ptx1. Activating protein-1 mediates GnRH-induced PKC signaling to stimulate FSHbeta gene expression. Therefore, divergent transcription factors are involved in GnRH stimulation of GTH subunit gene expression, and molecular mechanisms of GnRH stimulation may be partially conserved between sGTH IIbeta and mammalian LHbeta genes.