Prostaglandin F2 alpha potentiates cortisol production by stimulating 11 beta-hydroxysteroid dehydrogenase 1: A novel feedback loop that may contribute to human labor

In human pregnancy, cortisol and PGs are involved in the onset of labor and play an important role in the mechanisms leading to parturition. Recent st udies have shown that,at term, cortisol increases PG synthesis and decrease s PG metabolism in chorion trophoblast (CT) cells. In CT, 11 beta -hydroxys teroid oxidase type 1 (11 beta -HSD1) converts biologically inactive cortis one to cortisol to regulate cortisol availability. In the present study, we have investigated whether 11 beta -HSD1 activity could be influenced by PG s. We have shown that in CT, PGF(2 alpha) rapidly increased 11 beta -HSD1 r eductase activity in a dose-dependent manner via the PGF(2 alpha) receptor, localized in the fetal membranes. PGF(2 alpha) stimulated 11 beta -HSD1 ac tivity through increased intracellular calcium mobilization, activation of PKC, and the phosphorylation of the 11 beta -HSD enzyme. We propose that wi thin CT there is a novel feed forward loop by which PGF(2 alpha) acts to pr omote cortisol production from cortisone through increases in 11 beta -HSD1 , and this in turn leads to further net PG output for the onset of labor an d birth.