Human chorionic gonadotropin induces neuronal differentiation of PC12 cells through activation of stably expressed lutropin/choriogonadotropin receptor.

Human chorionic gonadotropin (hCG) and LH play an important role in reproductive physiology. Both hCG and LH bind to the same LH/choriogonadotropin receptor (LH/CG-R). Recent reports documented the temporal and spatial expression of LH/CG-R in the developing and mature mammalian brain. Administration of hCG promoted nerve regeneration in vivo and neurite outgrowth and survival of primary neurons in vitro. The function of hCG/LH and LH/CG-R in the nervous system remains unclear. In this study, we report that hCG/LH induced distinct morphological and biochemical changes, characteristic of neuronal differentiation, in PC12 cells stably expressing LH/CG-R and that the differentiation effect is ligand dose and time dependent. Western blot analysis revealed that both the ERKs and p38 MAPK are activated after hCG treatment. Inhibitor studies showed both the ERK and p38 MAPK signal transduction pathways are required for this differentiation process, which is cAMP dependent and protein kinase A independent. These findings imply a potential role for hCG/LH and LH/CG-R in the development, maintenance, and regeneration of the mammalian nervous system, and in the neuropathogenesis of genetic diseases caused by a mutated LH/CG-R.