Oxytocin Induced Glial Cell Proliferation via ERK 1/2 Phosphorylation

Objective: The aim of the present study was to investigate the effects of oxytocin (OXT) on glial cell proliferation and to determine if oxytocin induced ERK 1/2 phosphorylation affects cell proliferation. Background: Oxytocin is a neuropeptide that has been shown to stimulate proliferation of cells in culture and has been proposed that it plays a role in cellular development and protection. Previous studies suggest that the MAPK signaling cascade plays a crucial role in cell proliferation and that oxytocin-induced phosphorylation of ERK 1/2 is responsible for the growth and development of glial cells. In this study we used a human glioblastoma cell line (U-87MG) and developed an oxytocin receptor knockdown cell line (U-87MG KD) with the purpose of characterizing the effects of oxytocin on glial cell proliferation and viability. Methods: Human U-87MG and U-87MG KD cells were exposed to OXT, the OXTR antagonist L-371,257 (OXTA), and MEK 1/2 inhibitor PD98059 in a time and concentration-dependent manner and measured with a hemocytometer to determine the effects on cell proliferation and viability. Results: The exposure of U-87MG cells to oxytocin induced a time and concentration-dependent increase in cell proliferation whereas exposure to 1000nM L-371,257, an oxytocin receptor antagonist for 96 hours inhibited cell proliferation. However, the exposure of U-87MG KD cells to 100 or 1000nM oxytocin for 96 hours and 1000nM L-371,257 both inhibited cell proliferation. Furthermore, Oxytocin induced a time and concentration dependent increase in ERK 1/2 phosphorylation in U-87MG cells whereas ERK 1/2 phosphorylation was significantly inhibited in the U-87MG KD cells. Conclusion: Oxytocin stimulates cell proliferation of astrocytes via ERK 1/2 phosphorylation as demonstrated in the model of the human astroglial cell line U-87MG.