Melatonin Synergizes with Oxytocin to Enhance Contractility of Human Myometrial Smooth Muscle Cells

Nov 13, 2008The Journal of clinical endocrinology and metabolism

Melatonin and oxytocin work together to increase contractions in human uterine muscle cells

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Abstract

Melatonin (MEL) enhances oxytocin-induced contractility in human myometrial cells.

MEL may increase the contractility of myometrial cells through the type 2 melatonin receptor (MT2R).
MT2R expression is significantly higher in myometrial samples from women in labor compared to those not in labor.
MEL treatment is associated with an increase in the gap junction protein connexin 43, which could enhance cell communication.
In vitro assays indicate that MEL-treated cells show greater intercellular coupling, potentially mediated by MT2R.
The effects of MEL on contractility and gap junction activity may contribute to effective uterine contractions during labor.

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CONTEXT: Studies have shown that labor occurs primarily in the night/morning hours. Recently, we identified the human myometrium as a target for melatonin (MEL), the neuroendocrine output signal coding for circadian night.

OBJECTIVE: The purpose of this study was to determine the effects of MEL on contractility and the contractile machinery in telomerase-immortalized human myometrial cells.

DESIGN: To ascertain the effect of MEL on myometrial contractility in vitro, we performed gel retraction assays with cells exposed to iodomelatonin +/- oxytocin (OT). The effects of iodomelatonin on gap junctions were also investigated. Additionally, expression levels of the type 2 MEL receptor (MT2R) were assessed in myometrial biopsies from term pregnant women with or without labor.

RESULTS: MEL was found to synergistically enhance OT-induced contractility via the MT2R, which is coupled to a protein kinase C-dependent increase in phosphorylation of the myosin light chain protein. MT2R expression was markedly elevated in samples from pregnant women who had entered labor, as compared to matched nonlaboring pregnant women. MEL increased expression of the gap junction protein, connexin 43. In vitro dye spread assays showed that MEL-treated cells displayed substantially increased intercellular coupling. Increases in connexin 43 mRNA and cell to cell coupling were also found to be mediated via the MT2R in a protein kinase C-dependent manner.

CONCLUSIONS: MEL synergizes with OT to promote myometrial cell contractions and to facilitate gap junction activity in vitro. Such a synergy in vivo would promote coordinated and forceful contractions of the late term pregnant uterus necessary for parturition.

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Melatonin Synergizes with Oxytocin to Enhance Contractility of Human Myometrial Smooth Muscle Cells

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