Corticotropin-releasing hormone increases the expression of the prostaglandin E-2 receptor subtype EP1 in amnion WISH cells

The purpose of this study wits to investigate the effect of corticotropin-r eleasing hormone (CRH) on the expression of the prostaglandin (PC) E-2 EP1 receptor subtype and PGE(2) production in amnion WISH cells (AWC). AWC cult ures were incubated with CRH. Culture fluid was collected for PGE, measurem ent, and the cells were collected and analyzed for EP1 protein and mRNA. Im munohistochemical localization of the EP1 receptor was also performed. Incu bation of AWC with CRH resulted in a dose-dependent increase (r = 0.97) in the level of EP1 receptor protein (P < 0.001). Coincubation of AWC with CRH and indomethacin resulted in the decreased production of PGE(2) while havi ng no effect on EP1 receptor expression. A significant but not dose-depende nt increase in EP1 mRNA expression was also observed (P < 0.01). Immunohist ochemical evaluation verified cell membrane localization of the receptor in both stimulated and unstimulated cells and confirmed the increased express ion of EP1 receptor in response to CRH. Incubation of AWC with CRH also res ulted in increased culture fluid PGE(2) levels (P < 0.01). These results su ggest that the role CRH plays in the initiation of labor may also involve t he promotion of elevated PGE(2) levels and increased expression of the EP1 receptor in amnion.