Reorganization of myofilament proteins and decreased cGMP-dependent protein kinase in the human uterus during pregnancy

Excessive or premature contractions of uterine smooth muscle may contribute to preterm labor. Contractile stimuli induce myosin and actin filament int eractions through calcium-dependent myosin phosphorylation. The mechanisms that maintain myometrial quiescence until term are not well established, bu t may include control of calcium levels by nitric oxide and cGMP signaling and thin filament (caldesmon and calponin) regulation. Previously, we repor ted that myometrial tissues from pregnant rats are not responsive to cGMP d ue to decreases in cGMP-dependent protein kinase. Considering the well docu mented differences in the endocrinology of parturition among species, this study was conducted to test the hypothesis that the levels and subcellular distribution of caldesmon, calponin, and cGMP-dependent protein kinase are regulated with the hormonal milieu of human pregnancy. Whereas cGMP-depende nt protein kinase was significantly reduced in the human uterus during preg nancy, caldesmon expression was significantly increased, and both caldesmon and calponin were redistributed to a readily extractable subcellular pool. These data suggest that cGMP-dependent protein kinase does not mediate ges tational quiescence. Redistribution of thin filament-associated proteins, h owever, may alter uterine smooth muscle tone or the cytoskeletal framework of myocytes to maintain gestation despite the substantial distention that a ccompanies all intrauterine pregnancies.