Prostaglandin F2α potentiates cortisol production by stimulating 11β-hydroxysteroid dehydrogenase 1: A novel feedback loop that may contribute to human labor

Nadia Alfaidy, Zhigang G. Xiong, Leslie Myatt, Stephen J. Lye, John F. Macdonald, John R.G. Challis

Research output: Contribution to journalArticle

57 Scopus citations

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 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, PGF rapidly increased 11 β-HSD1 reductase activity in a dose-dependent manner via the PGF receptor, localized in the fetal membranes. PGF 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 PGF 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.

Original languageEnglish (US)
Pages (from-to)5585-5592
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number11
DOIs
StatePublished - Nov 28 2001

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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