Effect of progesterone on intracellular Ca2+ homeostasis in human myometrial smooth muscle cells

Victor P. Fomin, Blair E. Cox, R. Ann Word

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Although it is well known that progesterone alters uterine contractility and plays an important role in maintenance of pregnancy, the biochemical mechanisms by which progesterone alters uterine contractility in human gestation are less clear. In this investigation we sought to identify progesterone-induced adaptations in human myometrial smooth muscle cells that may alter Ca2+ signaling in response to contractile agents. Cells were treated with vehicle or the progesterone analog medroxyprogesterone acetate (MPA) for 5 days, and intracellular free Ca2+ concentration ([Ca2+](i)) was quantified after treatment with oxytocin (OX) or endothelin (ET)-1. OX- and ET-1-induced increases in [Ca2+](i) were significantly attenuated in cells pretreated with MPA in a dose-dependent manner. Progesterone receptor antagonists prevented the attenuated Ca2+ transients induced by MPA. ET(A) and ET(B) receptor subtypes were expressed in myometrial cells, and treatment with MPA resulted in significant downregulation of ET(A) and ET(B) receptor binding. MPA did not alter ionomycin-stimulated increases in [Ca2+](i) and had no effect on inositol trisphosphate-dependent or -independent release of Ca2+ from internal Ca2+ stores. We conclude that adaptations of Ca2+ homeostasis in myometrial cells during pregnancy may include progesterone- induced modification of receptor-mediated increases in [Ca2+](i).

Original languageEnglish (US)
Pages (from-to)C379-C385
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number2 45-2
DOIs
StatePublished - 1999

Keywords

  • Antiprogestin
  • Endothelin
  • Endothelin receptors
  • Medroxyprogesterone acetate
  • Oxytocin
  • Progesterone receptor
  • Uterus

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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