Figure 1.
GnRH-stimulated signaling pathways that regulate Fshb gene expression. When GnRH binds to its receptor (GnRHR), the receptor is activated and interacts either with Gαq/11 or Gαs to initiate intracellular signaling pathways that subsequently stimulate Fshb gene expression. The activation of Gαq/11 activates phospholipase C (PLC)β, which, in turn, results in generation of IP3 and DAG. IP3 mobilizes Ca2+ from endoplasmic reticulum stores. Further increase of intracellular Ca2+ is mediated by calcium influx through L-type voltage gated calcium channels (VGCC). The rise in calcium concentration stimulates several calcium-dependent cascades, including the calmodulin/calcineurin/NFAT pathway and the calmodulin/CaMK II pathway, resulting in increased Fshb gene expression. DAG formation leads to activation of PKC, which in turn activates the mitogen-activated protein kinase family (ERK1/2, JNK, p38) to further stimulate Fshb gene transcription. The activation of Gαs activates adenylyl cyclase (AC) and consequently activates the cAMP/PKA signaling pathway, which in turn leads to CREB phosphorylation and enhanced Fshb transcription. CaMK II, calcium/calmodulin-dependent kinase II; CREB, cAMP response element binding protein; MEK, MAPK kinase; NFAT, nuclear factor of activated T cells.