Effect of estradiol-17β on oxytocin-induced contraction of the three separate layers of human pregnant myometrium

Pinto, Roberto Martin; Lerner, U; Pontelli, H; Rabow, Wenceslao

doi:10.1016/0002-9378(67)90511-x

Cited by 22 publications

(11 citation statements)

References 13 publications

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“…Studies on various species have shown that E 2 increases the expression of genes in myometrial cells encoding gap junction proteins that form low-resistance connections between myometrial cells to promote synchronized contractions , Kilarski et al 1996, receptors for uterotonic hormones such as oxytocin and prostaglandin F 2a (PGF 2a ; Pinto et al 1966, 1967, Nissenson et al 1978, and enzymes such as PG-endoperoxide synthase-2 (PTGS2), the main inducible rate-limiting enzyme for PG synthesis (Mesiano et al 2002). Although it is generally accepted that these actions are mediated by estrogen receptors (ERs), the specific ERs and associated signaling pathways are not well characterized in the pregnant human myometrium.…”

Section: Introductionmentioning

confidence: 99%

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

Welsh

Johnson

et al. 2011

Journal of Endocrinology

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Estrogens are thought to promote labor by increasing the expression of pro-contraction genes in myometrial cells. The specific estrogen receptors ((ERs: ERa and ERb (also known as ESR1 and ESR2)) and G protein-coupled receptor 30 (GPR30; also known as G protein-coupled estrogen receptor 1)) and signaling pathways that mediate these actions are not clearly understood. In this study, we identified the ERs expressed in the pregnant human myometrium and determined a key extranuclear signaling pathway through which estradiol (E 2 ) modulates expression of the gene encoding the oxytocin receptor (OXTR), a major pro-contraction protein. Using quantitative RT-PCR, we found that ERa and GPR30 mRNAs were expressed in the human pregnant myometrium while ERb mRNA was virtually undetectable. While mRNA encoding ERa was the predominant ER transcript in the pregnant myometrium, ERa protein was largely undetectable in myometrial tissue by immunoblotting. Pharmacological inhibition of 26S proteasome activity increased ERa protein abundance to detectable levels in term myometrial explants, however, indicating rapid turnover of ERa protein by proteasomal processing in the pregnant myometrium. E 2 stimulated rapid extranuclear signaling in myometrial explants, as evidenced by increased extracellularly regulated kinase (ERK1/2) phosphorylation within 10 min. This effect was inhibited by pre-treatment with an ER antagonist, ICI 182 780, indicating the involvement of ERa. Inhibition of ERK signaling abrogated the ability of E 2 to stimulate OXTR gene expression in myometrial explants. We conclude that estrogenic actions in the human myometrium during pregnancy, including the stimulation of contraction-associated gene expression, can be mediated by extranuclear signaling through ERa via activation of the ERK/mitogen-activated protein kinase pathway.

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Section: Introductionmentioning

confidence: 99%

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

Welsh

Johnson

et al. 2011

Journal of Endocrinology

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“…In our experiments, the interme diate layer, rich in vascular tissue was dis carded. Previous studies [13,14] performed on isolated strips from the human uterus at the end of pregnancy showed different pat terns of spontaneous activity: amplitude and duration of contractions are larger in the inner than in the outer layers. Drug poten cies, especially with epinephrine, also differ in both layers.…”

Section: ß-Adrenergic Receptors In Human Pregnant Myometrium 35mentioning

confidence: 99%

Adrenergic Receptors in Inner and Outer Layers of Human Myometrium Near Term: Characterization of Beta-Adrenergic Receptor Sites by [<sup>125</sup>I]-Iodocyanopindolol Binding

Breuiller

Rouot

Leroy

et al. 1987

Gynecol Obstet Invest

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The Β-adrenergic receptors present in inner and outer layers of human myometrium near term were characterized using the radioiodinated antagonist iodocyanopindolol (ICYP). In both layers ICYP binding is saturable, rapidly reversible, stereoselective, and appears to occur in a single class of sites with a K_D of 30 pmol/l. Adrenergic agonists compete for ICYP binding sites with an order of potency consistent with Β₂-adrenergic potencies: isoproterenol > epinephrine > > norepinephrine. Studies in which CGP 20712 A, a Β₁ adrenergic antagonist, competes for ICYP binding sites in human myometrium reveal that at least 65% of the Β-receptors present are Β₂-subtype, whatever the layer considered. At the 35th week of pregnancy, the density of Β-adrenergic receptors in the inner layer (15.2 fmol/mg of protein) is about 50% higher than in the outer layer. At term, the densities of Β-adrenergic receptors are reduced and exhibit the same values for both layers (5 fmol/mg of protein). These results indicate that the Β-adrenergic receptors in the two layers diminish during pregnancy and reach, at term, an equal and low level of density.

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“…The discrepancies we observed were probably due to the fact that in these previous studies the particulate membrane fraction was pre pared from a whole myometrium without separating the main muscular layers. In the human term myometrium, longitudinal and circular layers show distinct patterns of spontaneous activity and different responses to some contracting or relaxing agents, the sensitivity of the circular layer being gener ally higher than that of the longitudinal layer [11,12]. It appears that uterine contractility occurs predominantly in the circular layer at the time of parturition.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the present study provides the first demonstration that cb-adrenoceptors are indeed present in both the longitudinal and circular layers. Al though often considered to be a homoge neous tissue, myometrium of various species (including human) consists in fact of three layers with different embryological origin and structure [11,13]. Our biopsy samples, free of the medial vascular layer, are only excised from the circular and the longitudi nal layers that contain, near term, a high pro portion of smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

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Different α<sub>2</sub>-Adrenoceptor Densities in the Circular and Longitudinal Layers of Human Near-Term Myometrium as Revealed by [³H]-Idazoxan Binding Studies

Breuiller

Rouot²,

Leroy³

et al. 1988

Gynecol Obstet Invest

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[³H]-idazoxan, a specific Α₂-adrenoceptor antagonist radioligand, has been used to characterize Α₂-adrenoceptors in both circular and longitudinal layers of human near-term myometrium. [³H]-idazoxan binding is reversible, saturable and stereospecific. It labels with high affinity a single population of sites. Competition curves with different Α₂-adrenoceptor agonists and antagonists show that the binding sites labelled with [³H]-idazoxan have the pharmacological characteristics of Α₂-adrenoceptors. Though the KD value is similar in both layers (∼7 nM), the density of Α₂-adrenoceptors in the circular layer (324 ± 21 fmol/mg of protein) is significantly higher than in the longitudinal one (183 ± 48 fmol/mg of protein).

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Effect of estradiol-17β on oxytocin-induced contraction of the three separate layers of human pregnant myometrium

Cited by 22 publications

References 13 publications

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

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

Adrenergic Receptors in Inner and Outer Layers of Human Myometrium Near Term: Characterization of Beta-Adrenergic Receptor Sites by [<sup>125</sup>I]-Iodocyanopindolol Binding

Different α<sub>2</sub>-Adrenoceptor Densities in the Circular and Longitudinal Layers of Human Near-Term Myometrium as Revealed by [³H]-Idazoxan Binding Studies

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Effect of estradiol-17β on oxytocin-induced contraction of the three separate layers of human pregnant myometrium

Cited by 22 publications

References 13 publications

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

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

Adrenergic Receptors in Inner and Outer Layers of Human Myometrium Near Term: Characterization of Beta-Adrenergic Receptor Sites by [<sup>125</sup>I]-Iodocyanopindolol Binding

Different &alpha;<sub>2</sub>-Adrenoceptor Densities in the Circular and Longitudinal Layers of Human Near-Term Myometrium as Revealed by [3H]-Idazoxan Binding Studies

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Different α<sub>2</sub>-Adrenoceptor Densities in the Circular and Longitudinal Layers of Human Near-Term Myometrium as Revealed by [³H]-Idazoxan Binding Studies