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 β-hydroxysteroid oxidase type 1 (11 β-HSD1) converts biologically inactive cortisone to cortisol to regulate cortisol availability. In the present study, we have investigated whether 11 β-HSD1 activity could be influenced by PGs. We have shown that in CT, PGF2α rapidly increased 11 β-HSD1 reductase activity in a dose-dependent manner via the PGF2α receptor, localized in the fetal membranes. PGF2α stimulated 11 β-HSD1 activity through increased intracellular calcium mobilization, activation of PKC, and the phosphorylation of the 11 β-HSD enzyme. We propose that within CT there is a novel feed forward loop by which PGF2α acts to promote cortisol production from cortisone through increases in 11β-HSD1, and this in turn leads to further net PG output for the onset of labor and birth.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical