Cortisol blockade of progesterone: A possible molecular mechanism involved in the initiation of human labor

Abstract

In most mammals, labor is heralded by progesterone withdrawal, which is believed to be related to the activation of multiple pathways leading to parturition. In humans, despite no decrease in placental progesterone production, activation of similar pathways preceding labor suggests the presence of an endogenous antiprogestin, which we reasoned might be cortisol, whose secretion from the fetal adrenal rises markedly at the end of human gestation. We report that in primary cultures of human placenta, cortisol is able to compete with the action of progesterone in the regulation of the corticotropin-releasing hormone (CRH) gene. CRH is a peptide highly expressed in human placenta at the end of gestation, which has been suggested to be involved in regulating the timing of parturition. These findings provide a model for functional progesterone withdrawal at the end of human pregnancy, which may be involved in the initiation of labor.

Saliva Estriol Levels in Women with and Without Prenatal Antidepressant Treatment

“…The resulting increased DHEAS from the fetal zone of the adrenal gland would lead to increased estriol, further stimulating 11 beta hydroxysteroid dehydrogenase. Further positive feedback could also result as increased cortisol from the definitive zone of the fetal gland competes with progesterone for sites on placental glucocorticoid receptors, removing the potential inhibitory effect of progesterone on placental CRH release (25), and increasing stimulation of the fetal pituitary. The estrogen dominant milieu created by the increase in estriol would result in conditions favoring labor, including the induction of uterine oxytocin receptors, myometrial gap junction proteins, and prostaglandin synthetases (26)(27)(28).…”

NF-κB Participates in the Corticotropin-releasing, Hormone-induced Regulation of the Pituitary Proopiomelanocortin Gene

“…Cells were isolated 18 h later and RNA was extracted, as we have previously reported, by using Trizol reagent (Sigma). RNA (10 g) was separated on a 1.4% formaldehyde agarose gel and transferred to GeneScreen (PerkinElmer Life Sciences) following standard protocols (12). A complementary RNA POMC riboprobe was labeled with [␣-32 P]UTP (PerkinElmer Life Sciences) and T7 polymerase, as previously described (13).…”

Role of glucocorticoid receptor and CCAAT/enhancer-binding protein α in the feed-forward induction of 11β-hydroxysteroid dehydrogenase type 1 expression by cortisol in human amnion fibroblasts

“…The placenta, fetal membranes, and the fetus are all GC targets during pregnancy. GCs have been shown to stimulate rather than inhibit prostaglandin and corticotrophin-releasing hormone production in human fetal membranes and placenta (Casey et al 1985, Potestio et al 1988, Karalis et al 1996, King et al 2002. These paradoxical effects of GCs on human fetal membranes and placenta are believed to be part of the positive feedback loops involved in human parturition (Whittle et al 2001).…”