Uterine stretch and progesterone action

Abstract

Context: Progesterone administration reduces the risk of preterm labor in high-risk women with singleton pregnancies but has no effect in women with a multiple pregnancy. Objective: We investigated whether progesterone is able to inhibit stretch-induced gene expression and/or whether stretch in turn inhibits progesterone action, perhaps providing an explanation for the functional progesterone withdrawal associated with human labor. Methods and Results: In a series of in vitro studies using primary cultures of human myometrial cells, we found that preincubation with progesterone did not block stretch-induced ERK1/2 activation and cyclooxygenase-2 mRNA expression. Furthermore, we found that stretch did not alter the ability of progesterone to: 1) modulate progesterone-responsive gene expression; 2) activate a luciferase-linked progesterone response element; or 3) repress IL-1β-driven cyclooxygenase-2 mRNA expression. We did find that stretch reduced the expression of progesterone receptor mRNA via nuclear factor κB activation but that this did not alter myometrial progesterone response. Conclusion: These data show that progesterone does not inhibit stretch-induced MAPK activation or gene expression, possibly explaining why progesterone is ineffective in the prevention of preterm labor in multiple pregnancy. Although stretch did reduce progesterone receptor expression in a nuclear factor κB-dependent manner, this was not sufficient to inhibit progesterone action, suggesting that it is not responsible for the functional progesterone withdrawal observed with the onset of human labor. Copyright © 2011 by The Endocrine Society.