Intrauterine growth retardation affects expression and epigenetic characteristics of the rat hippocampal glucocorticoid receptor gene

2010 ◽  
Vol 42 (2) ◽  
pp. 177-189 ◽  
Author(s):  
Xingrao Ke ◽  
Michelle E. Schober ◽  
Robert A. McKnight ◽  
Shannon O'Grady ◽  
Diana Caprau ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Growth Retardation ◽  
Intrauterine Growth Retardation ◽  
Receptor Gene ◽  
Altered Expression ◽  
Time Points ◽  
Intrauterine Growth ◽  
Mrna Variant ◽  
Glucocorticoid Receptor Gene

Studies in humans and rats suggest that intrauterine growth retardation (IUGR) permanently resets the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis reprogramming may involve persistently altered expression of the hippocampal glucocorticoid receptor (hpGR), an important regulator of HPA axis reactivity. Persistent alteration of gene expression, long after the inciting event, is thought to be mediated by epigenetic mechanisms that affect mRNA and mRNA variant expression. GR mRNA variants in both humans and rats include eleven 5′-end variants and GRα, the predominant 3′-end variant. The 3′-end variants associated with glucocorticoid resistance in humans (GRβ, GRγ, GRA, and GRP) have not been reported in rats. We hypothesized that in the rat hippocampus IUGR would decrease total GR mRNA, increase GRβ, GRγ, GRA, and GRP, and affect epigenetics of the GR gene at birth (D0) and at 21 days of life (D21). IUGR increased hpGR and exon 1.7 hpGR mRNA in males at D0 and D21, associated with increased trimethyl H3/K4 at exon 1.7 at both time points. IUGR also increased hpGRγ in males at D0 and D21, associated with increased acetyl H3/K9 at exon 3 at both time points. hpGRA increased in female IUGR rats at D0 and D21. In addition, our data support the existence of hpGRβ and hpGRP in the rat. IUGR has sex-specific, persistent effects on GR expression and its histone code. We speculate that postnatal changes in hippocampal GR variant and total mRNA expression may underlie IUGR-associated HPA axis reprogramming.

scholarly journals Early life trauma, depression and the glucocorticoid receptor gene – an epigenetic perspective

2015 ◽  
Vol 45 (16) ◽  
pp. 3393-3410 ◽  
Author(s):  
C. Smart ◽  
G. Strathdee ◽  
S. Watson ◽  
C. Murgatroyd ◽  
R. H. McAllister-Williams
Keyword(s):  
Dna Methylation ◽  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Early Life ◽  
Epigenetic Modification ◽  
Receptor Gene ◽  
Unipolar Depression ◽  
Tissue Cell ◽  
Glucocorticoid Receptor Gene ◽  
Early Life Trauma

Background.Hopes to identify genetic susceptibility loci accounting for the heritability seen in unipolar depression have not been fully realized. Family history remains the ‘gold standard’ for both risk stratification and prognosis in complex phenotypes such as depression. Meanwhile, the physiological mechanisms underlying life-event triggers for depression remain opaque. Epigenetics, comprising heritable changes in gene expression other than alterations of the nucleotide sequence, may offer a way to deepen our understanding of the aetiology and pathophysiology of unipolar depression and optimize treatments. A heuristic target for exploring the relevance of epigenetic changes in unipolar depression is the hypothalamic–pituitary–adrenal (HPA) axis. The glucocorticoid receptor (GR) gene (NR3C1) has been found to be susceptible to epigenetic modification, specifically DNA methylation, in the context of environmental stress such as early life trauma, which is an established risk for depression later in life.Method.In this paper we discuss the progress that has been made by studies that have investigated the relationship between depression, early trauma, the HPA axis and the NR3C1 gene. Difficulties with the design of these studies are also explored.Results.Future efforts will need to comprehensively address epigenetic natural histories at the population, tissue, cell and gene levels. The complex interactions between the epigenome, genome and environment, as well as ongoing nosological difficulties, also pose significant challenges.Conclusions.The work that has been done so far is nevertheless encouraging and suggests potential mechanistic and biomarker roles for differential DNA methylation patterns in NR3C1 as well as novel therapeutic targets.

Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents. The TRAILS study

2015 ◽  
Vol 58 ◽  
pp. 46-50 ◽  
Author(s):  
Lisette J. van der Knaap ◽  
Albertine J. Oldehinkel ◽  
Frank C. Verhulst ◽  
Floor V.A. van Oort ◽  
Harriëtte Riese
Keyword(s):  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Receptor Gene ◽  
Gene Methylation ◽  
Glucocorticoid Receptor Gene

Imbalance in the system L-arginin-NO in pathogenesis of obstetric complications and intrauterine growth retardation (Literature review)

2016 ◽  
pp. 43-47
Author(s):  
O.V. Basystyi ◽  
Keyword(s):  
Nitric Oxide ◽  
Literature Review ◽  
Growth Retardation ◽  
Intrauterine Growth Retardation ◽  
Obstetric Complications ◽  
Pathogenetic Role ◽  
Intrauterine Growth ◽  
System L ◽  
Nitric Oxide Deficiency

The data of domestic and foreign literature on etiology, pathogenesis and intrauterine growth retardation diagnosis are presented in the paper. It highlights pathogenetic role of nitric oxide deficiency in case of obstetric complications and intrauterine growth retardation. Key words: intrauterine growth retardation (IUGR), system L-arginin–NO, obstetric complications.

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