HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/R1348    most recent 00211.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Baserga, M. Articles by Lane, R. H. Search for Related Content PubMed PubMed Citation Articles by Baserga, M. Articles by Lane, R. H.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Uteroplacental insufficiency alters hepatic expression, phosphorylation, and activity of the glucocorticoid receptor in fetal IUGR rats

University of Utah School of Medicine, Department of Pediatrics, Division of Neonatology, Salt Lake City, Utah

Submitted 25 March 2005 ; accepted in final form 29 June 2005

Uteroplacental insufficiency (UPI) induces persistent changes in hepatic gene expression secondary to altered chromatin dynamics in the intrauterine growth- restricted (IUGR) rat liver. The glucocorticoid receptor (GR) is a transcription factor that when activated can induce changes in chromatin structure. To begin the process of identifying pathways by which IUGR affects chromatin structure, we hypothesized that UPI in the rat induces a significant increase in endogenous glucocorticoids (corticosterone) and increases GR expression and activation. To prove our hypothesis, we induced IUGR through bilateral uterine artery ligation of the pregnant rat. At day 1, UPI significantly increased corticosterone levels and was associated with increased total GR mRNA and protein levels in the liver, as well as increased hepatic phosphorylation of GR serine 211. Moreover, cyclin-dependent kinase 2 (CDK2) cyclinA/CDK2 protein levels, which selectively phosphorylate GR serine 211, were also significantly increased. To assess activity of the GR, we measured protein levels of the transcription factor p53 whose levels are downregulated, at least in part, by active GR. In this study, UPI decreased p53 protein and its downstream target Bax mRNA levels. We conclude that UPI in rats affects GR expression and activity in the liver. We speculate that these alterations early in life may contribute to the changes in chromatin structure and gene expression previously described in the IUGR liver.

11 -hydroxysteroid dehydrogenase type 1; cyclin A; cyclin-dependent kinase 2; phosphoglucocorticoid receptor (serine 211)

This article has been cited by other articles:

				K. L. Gatford, J. A. Owens, S. Li, T. J. M. Moss, J. P. Newnham, J. R. G. Challis, and D. M. Sloboda Repeated betamethasone treatment of pregnant sheep programs persistent reductions in circulating IGF-I and IGF-binding proteins in progeny Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E170 - E178. [Abstract] [Full Text] [PDF]

				R. Lane and M. Baserga Response to Schreuder Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R2160 - R2160. [Full Text] [PDF]

				M. Baserga, M. A. Hale, Z. M. Wang, X. Yu, C. W. Callaway, R. A. McKnight, and R. H. Lane Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1943 - R1955. [Abstract] [Full Text] [PDF]