Oestriol and oestradiol increase cell to cell communication and connexin43 protein expression in human myometrium

Abstract

Oestradiol increases the protein expression of connexin43 (Cx43) gap junctions in myometrium but the effect of oestriol on gap junction expression has not been described previously. Oestriol is the most abundant free oestrogen in pregnant women and there is a marked surge in oestriol concentrations before term and idiopathic preterm labour. In order to determine whether oestriol may have a physiological action on the myometrium, cultured human myometrial cells obtained from non-pregnant hysterectomy specimens were exposed to 10 nmol/l oestradiol or oestriol. Intercellular communication between myometrial cells was investigated by microinjection of confluent cultured cells with the gap junction-permeant tracer Cascade Blue. There was a progressive increase in coupling after exposure to oestradiol or oestriol (P < 0.0005). An increase in Cx43 protein expression was demonstrated by immunocytochemistry after 1 h (P < 0.01) and 3 days (P < 0.01) exposure, and by Western blotting after 1 h (P < 0.01) and 3 days (P < 0.05) exposure, to both oestradiol and to oestriol. We conclude that oestriol increases gap junction communication in human myometrium by increasing gap junction expression. Elevated oestriol concentrations may thus play a role in the initiation of labour in women, by increasing cell-cell communication in the myometrium.

Estrogen receptor (ER) expression and function in the pregnant human myometrium: estradiol via ERα activates ERK1/2 signaling in term myometrium

“…Although estrogens are known to induce myometrial contractions and labor in animal species such as the sheep (Wu et al 2004) and to promote the expression and/or function of contraction-associated proteins in human myometrial smooth muscle cells (Di et al 2001, Knock et al 2001, the genomic targets and signaling pathways controlled by estrogens in the pregnant uterus are poorly understood. Considering the importance of estrogen sensitivity in regulating the contractile capacity of the myometrium, it is surprising that ER expression in the human pregnant myometrium has not been systematically characterized.…”

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

“…More recently, the functional consequences of this inhibitory activity have been highlighted in APOE KO mice (a model of atherosclerosis) also deleted for Cx37, where lesion formation was substantially enhanced (Wong et al 2006). Several studies clearly demonstrate that the expression of Cx37, Cx40, and Cx43 are all regulated by estrogen (Di et al 2001, Punyadeera et al 2005, and it is likely that this regulation, to some extent, underlies the effects of female sex hormones on leukocyte recruitment, such that the enhancement of expression of the gap junctions may in part mediate the decreased inflammatory cell recruitment evident in female animal models of inflammation.…”

A Dominant Loss-of-Function GJA1 (Cx43) Mutant Impairs Parturition in the Mouse1

“…Cx43 expression is suppressed by progesterone and elevated by estrogen [10][11][12]. It is believed that the d ownregulation of Cx43 by progesterone maintains the myometrium in a quiescent state during pregnancy, avoiding muscle contraction that could lead to premature labor.…”