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.

progesterone receptor; endothelin receptors; uterus; endothelin; oxytocin; antiprogestin; medroxyprogesterone acetate

This article has been cited by other articles:

				X. Wu, H. Shen, L. Yu, M. Peng, W.-S. Lai, and Y.-L. Ding Corticotropin-releasing hormone activates connexin 43 via activator protein-1 transcription factor in human myometrial smooth muscle cells Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1789 - E1794. [Abstract] [Full Text] [PDF]

				Z.-L. Xiao, W. Cao, P. Biancani, and J. Behar Nongenomic effects of progesterone on the contraction of muscle cells from the guinea pig colon Am J Physiol Gastrointest Liver Physiol, May 1, 2006; 290(5): 1008 - 1015. [Abstract] [Full Text] [PDF]

				D. Xiao and L. Zhang Adaptation of uterine artery thick- and thin-filament regulatory pathways to pregnancy Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H142 - H148. [Abstract] [Full Text] [PDF]

				D. Xiao, X. Huang, W. J. Pearce, L. D. Longo, and L. Zhang Effect of cortisol on norepinephrine-mediated contractions in ovine uterine arteries Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1142 - H1151. [Abstract] [Full Text] [PDF]

				J. Condon, S. Yin, B. Mayhew, R. A. Word, W.E. Wright, J.W. Shay, and W. E. Rainey Telomerase Immortalization of Human Myometrial Cells Biol Reprod, August 1, 2002; 67(2): 506 - 514. [Abstract] [Full Text] [PDF]

				J.J. Peluso, G. Fernandez, A. Pappalardo, and B.A. White Characterization of a Putative Membrane Receptor for Progesterone in Rat Granulosa Cells Biol Reprod, July 1, 2001; 65(1): 94 - 101. [Abstract] [Full Text] [PDF]