Journal article
Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice
American journal of physiology: endocrinology and metabolism, Vol.301(2), pp.E362-E369
08/2011
DOI: 10.1152/ajpendo.00696.2010
PMCID: PMC3154528
PMID: 21558549
Abstract
In late gestation, enhanced myometrial contractility is mediated in part through increased Rho/Rho kinase. Since leptin, which is elevated in pregnancy and obesity, can directly depress myometrial function, we hypothesized that in leptin receptor-deficient mice, myometrial contractility would be greater in late pregnancy due to increased Rho/Rho kinase activity. To test this, we correlated RhoA and Rho kinase expression to contractility in myometrium from nonpregnant (NP) and late-pregnant (P18) heterozygous leptin receptor-deficient mice (
db/
+) vs. wild-type (WT) mice. In NP mice, KCl-induced contractions were similar between WT and
db/
+ myometrium. However, the Rho kinase-dependent component of the contractions was greater in
db/
+ mice, along with an increased expression of Rho kinase. KCl-induced contractions increased in strength in myometrium from P18 WT and
db/
+ compared with NP. Although the contribution of Rho kinase to contractions was unchanged in P18 WT mice, it was decreased in P18
db/
+ mice. The decrease in Rho kinase-dependent contractions in P18
db/
+ mice coincided with reduced RhoA and Rho kinase expression relative to NP
db/
+. Addition of high-fat-induced abnormal glucose utilization prevented changes in Rho kinase function. We conclude that abnormal leptin signaling increases expression and function of Rho kinase to maintain contractile function in NP myometrium and that during pregnancy the contribution of RhoA and Rho kinase expression to myometrial function is reduced despite an increase in myometrial contractility. Thus, other signaling mechanisms appear to compensate when leptin signaling is reduced to maintain contractile function during pregnancy.
Details
- Title: Subtitle
- Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice
- Creators
- Jeremy S Harrod - Iowa City Veterans Affairs Health Care System and theCara C Rada - Molecular Physiology and Biophysics, andStephanie L Pierce - Molecular Physiology and Biophysics, andSarah K England - Molecular Physiology and Biophysics, andKathryn G Lamping - Iowa City Veterans Affairs Health Care System and the
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: endocrinology and metabolism, Vol.301(2), pp.E362-E369
- DOI
- 10.1152/ajpendo.00696.2010
- PMID
- 21558549
- PMCID
- PMC3154528
- NLM abbreviation
- Am J Physiol Endocrinol Metab
- ISSN
- 0193-1849
- eISSN
- 1522-1555
- Publisher
- American Physiological Society
- Language
- English
- Date published
- 08/2011
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984094611202771
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