FIGURE 4.

Signaling pathways in the homologous up-regulation of the mouse GnRHR promoter by GnRH in gonadotrope and non-gonadotrope cells. In αT3−1 cells, GnRH-induced activation of the PKC-dependent pathway stimulates promoter activity through the MAP kinase signaling pathway, involving ERK1 and ERK2. Receptor-independent activation of the PKA-dependent pathway inhibits GnRH-stimulated promoter activity. In GGH3 cells, GnRH induces the simultaneous activation of the PKC and PKA-dependent pathways for stimulating promoter activity. Constitutive activation of the MAP kinase signaling pathway, involving ERK1 and ERK2, inhibits basal and GnRH-stimulated promoter activity. The three elements, SURG−1, SURG−2, and CRE therefore participate in GnRH up-regulation in both αT3−1 and GGH3 cells. In αT3−1 cells, the positive involvement of SURG−1 and SURG−2 have been demonstrated whereas that of the CRE element is only suspected to be inhibitory. In GGH3 cells, the CRE element is required for promoter stimulation and appears as the ultimate target of the PKA-dependent pathway. AP1, also referred to as SURG−2 is only potentially involved essentially because GnRH also activates the PKC-dependent signaling pathway in these cells.