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 interactions through calcium-dependent myosin phosphorylation. The mechanisms that maintain myometrial quiescence until term are not well established, but may include control of calcium levels by nitric oxide and cGMP signaling and thin filament (caldesmon and calponin) regulation. Previously, we reported that myometrial tissues from pregnant rats are not responsive to cGMP due to decreases in cGMP-dependent protein kinase. Considering the well documented 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-dependent protein kinase was significantly reduced in the human uterus during pregnancy, 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 gestational quiescence. Redistribution of thin filament-associated proteins, however, may alter uterine smooth muscle tone or the cytoskeletal framework of myocytes to maintain gestation despite the substantial distention that accompanies all intrauterine pregnancies.
Cornwell
T L
TL
Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama, Birmingham, Alabama 35294-0019, USA. cornwell@path.uab.edu
Li
J
J
Sellak
H
H
Miller
R T
RT
Word
R A
RA
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000328:Adult; D000368:Aged; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins; D008875:Middle Aged; D009215:Myometrium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy / Q000502:physiology*; D044469:Racial Groups; D051381:Rats; D012016:Reference Values; D014481:United States; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000473:pathology*; D014599:Uterus / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D000096985:Calponins
D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D017869:Cyclic GMP-Dependent Protein Kinases; D008840:Microfilament Proteins; D000096985:Calponins