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 Ca2signaling pathways. Recent numerous reports on signal transduction pathways which are involved in GnRH stimulation of mammalian GTH subunit genes show ed differential sensitivity of GTH subunit genes to the two signaling pathw ays. Our recent studies on salmon GTH (sGTH) II beta subunit gene showed th at its stimulation by GnRH is dependent on the PKC pathway. Furthermore, ge l retardation and mutagenesis studies suggested that pituitary homeo box 1 (Ptx1) and Sp1 mediate the GnRH-induced PKC signaling on the sGTHII beta ge ne. However, both PKC and Ca2+ pathways are involved in the GnRH-stimulated GTH alpha and LH beta genes. Different preference to the pathways were oft en reported in a certain GTH subunit gene in different circumstances, sugge sting that molecular targets of the two signaling pathways are different. E ts-related factor and cAMP response element binding protein have been propo sed as targets of GnRH signaling on GTH alpha genes. Sp1 and early growth r esponse protein 1 play pivotal roles in GnRH-stimulated LHP gene expression in synergism with steroidogenic factor-1 and Ptx1. Activating protein-1 me diates GnRH-induced PKC signaling to stimulate FSH beta gene expression. Th erefore, divergent transcription factors are involved in GnRH stimulation o f GTH subunit gene expression, and molecular mechanisms of GnRH stimulation may be partially conserved between sGTH II beta and mammalian LH beta gene s. (C) 2001 Elsevier Science Inc. All rights reserved.