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Prostaglandin F2 Potentiates Cortisol Production by Stimulating 11ß-Hydroxysteroid Dehydrogenase 1: A Novel Feedback Loop That May Contribute to Human Labor

CIHR Group in Fetal and Neonatal Health and Development (N.A., S.J.L., J.R.G.C.) and Departments of Physiology (N.A., Z.G.X., S.J.L., J.F.M., J.R.G.C.) and Obstetrics and Gynecology (S.J.L., J.R.G.C.), University of Toronto, Toronto, Ontario, Canada M5S 1A8; Department of Obstetrics and Gynecology, University of Cincinnati, Cincinnati College of Medicine (L.M.), Cincinnati, Ohio; and Mt. Sinai Hospital (S.J.L., J.R.G.C.), Samuel Lunenfeld Research Institute, CIHR Group in Development and Fetal Health, Toronto, Ontario M5G 1X5, Canada

Address all correspondence and requests for reprints to: Dr. Nadia Alfaidy, Department of Physiology, University of Toronto, 1 King’s College Circle, Toronto, Ontario M5S 1A8, Canada.

Abstract

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 studies have shown that at term, cortisol increases PG synthesis and decreases PG metabolism in chorion trophoblast (CT) cells. In CT, 11 ß-hydroxysteroid oxidase type 1 (11 ß-HSD1) converts biologically inactive cortisone to cortisol to regulate cortisol availability. In the present study, we have investigated whether 11 ß-HSD1 activity could be influenced by PGs. We have shown that in CT, PGF₂ rapidly increased 11 ß-HSD1 reductase activity in a dose-dependent manner via the PGF₂ receptor, localized in the fetal membranes. PGF₂ stimulated 11 ß-HSD1 activity through increased intracellular calcium mobilization, activation of PKC, and the phosphorylation of the 11 ß-HSD enzyme. We propose that within CT there is a novel feed forward loop by which PGF₂ acts to promote cortisol production from cortisone through increases in 11ß-HSD1, and this in turn leads to further net PG output for the onset of labor and birth.

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