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

Although it is well known that progesterone alters uterine contractility an d plays an important role in maintenance of pregnancy, the biochemical mech anisms by which progesterone alters uterine contractility in human gestatio n 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 v ehicle or the progesterone analog medroxyprogesterone acetate (MPA) for 5 d ays, and intracellular free Ca2+ concentration ([Ca2+](i)) was quantified a fter treatment with oxytocin (OX) or endothelin (ET)-1. OX- and ET-1-induce d increases in [Ca2+](i) were significantly attenuated in cells pretreated with MPA in a dose-dependent manner Progesterone receptor antagonists preve nted the attenuated Ca2+ transients induced by MPA. ETA and ETB receptor su btypes were expressed in myometrial cells, and treatment with MPA resulted in significant downregulation of ETA and ETB receptor binding. MPA did not alter ionomycin-stimulated increases in [Ca2+](i) and had no effect on inos itol 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 re ceptor-mediated increases in [Ca2+](i).