Effect of progesterone on intracellular Ca2+ homeostasis in human myometrial smooth muscle cells |
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Authors: | Fomin Victor P; Cox Blair E; Word R Ann |
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Abstract: | Although it iswell known that progesterone alters uterine contractility and plays animportant role in maintenance of pregnancy, the biochemical mechanismsby which progesterone alters uterine contractility in human gestationare less clear. In this investigation we sought to identifyprogesterone-induced adaptations in human myometrial smooth musclecells that may alter Ca2+signaling in response to contractile agents. Cells were treated withvehicle or the progesterone analog medroxyprogesterone acetate (MPA)for 5 days, and intracellular freeCa2+ concentration(Ca2+]i)was quantified after treatment with oxytocin (OX) or endothelin (ET)-1.OX- and ET-1-induced increases inCa2+]iwere significantly attenuated in cells pretreated with MPA in adose-dependent manner. Progesterone receptor antagonists prevented theattenuated Ca2+ transients inducedby MPA. ETA andETB receptor subtypes were expressed in myometrial cells, and treatment with MPA resulted insignificant downregulation of ETAand ETB receptor binding. MPA didnot alter ionomycin-stimulated increases inCa2+]iand had no effect on inositol trisphosphate-dependent or -independent release of Ca2+ from internalCa2+ stores. We conclude thatadaptations of Ca2+ homeostasis inmyometrial cells during pregnancy may include progesterone-inducedmodification of receptor-mediated increases inCa2+]i. |
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