Prostaglandin F2alpha potentiates cortisol production by stimulating 11beta-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 studies have shown that at term, cortisol increases PG synthesis and decreases PG metabolism in chorion trophoblast (CT) cells. In CT, 11 beta-hydroxysteroid oxidase type 1 (11 beta-HSD1) converts biologically inactive cortisone to cortisol to regulate cortisol availability. In the present study, we have investigated whether 11 beta-HSD1 activity could be influenced by PGs. We have shown that in CT, PGF2alpha rapidly increased 11 beta-HSD1 reductase activity in a dose-dependent manner via the PGF2alpha receptor, localized in the fetal membranes. PGF2alpha stimulated 11 beta-HSD1 activity through increased intracellular calcium mobilization, activation of PKC, and the phosphorylation of the 11 beta-HSD enzyme. We propose that within CT there is a novel feed forward loop by which PGF2alpha acts to promote cortisol production from cortisone through increases in 11beta-HSD1, and this in turn leads to further net PG output for the onset of labor and birth.
Alfaidy
N
N
CIHR Group in Fetal and Neonatal Health and Development, University of Toronto, Toronto, Ontario, Canada M5S 1A8. n.alfaidy@utoronto.ca
Xiong
Z G
ZG
Myatt
L
L
Lye
S J
SJ
MacDonald
J F
JF
Challis
J R
JR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology*; D005246:Feedback / Q000502:physiology; D005260:Female; D005333:Fetus / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis*; D006913:Hydroxysteroid Dehydrogenases / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007743:Labor, Obstetric / Q000502:physiology*; D008186:Luteolytic Agents / Q000494:pharmacology; D008566:Membranes / Q000378:metabolism; D011233:Precipitin Tests; D011247:Pregnancy; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000378:metabolism; D013268:Stimulation, Chemical; D014327:Trophoblasts / Q000378:metabolism
D005456:Fluorescent Dyes; D008186:Luteolytic Agents; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; C006326:fluprostenol; D015237:Dinoprost; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002118:Calcium; D016257:Fura-2; D006854:Hydrocortisone