Glucocorticoid receptor polymorphisms and haplotypes and their expression in health and disease

Koper, Jan W.; Rossum, Elisabeth F.C. van; Akker, Erica L T van den

doi:10.1016/j.steroids.2014.07.015

Cited by 91 publications

(92 citation statements)

References 106 publications

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“…Cortisol is the classic endocrine hormone secreted in response to stress (Sapolsky et al, 2000) and is the natural ligand for GRα, which is present on almost all cell types (Koper et al, 2014). CXCL8 is a pro-inflammatory chemokine secreted by monocytes, neutrophils, natural killer cells, T lymphocytes and endothelium cells (Hoffmann et al, 2002).…”

Section: Figurementioning

confidence: 99%

Characterisation of haematological profiles and whole blood relative gene expression levels in Holstein-Friesian and Jersey bull calves undergoing gradual weaning

Johnston

Kenny

Kelly

et al. 2016

animal

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Haematological profiles indicate the health status of an animal and can be used to identify sub-clinical stress responses. The objectives of the study were to examine (i) the effect of breed and plane of nutrition, on haematological profiles of artificially reared Holstein-Friesian and Jersey bull calves in response to gradual weaning, and (ii) the effect of breed on immune response genes in bovine whole blood using real-time quantitative PCR. Holstein-Friesian and Jersey bull calves were group housed indoors and individually fed using an automatic feeder. They were allocated to a high, medium or low plane of nutrition, based on milk replacer (MR) and concentrate. The nutrition treatments were calculated using National Research Council guidelines in order to achieve a high, medium or low growth rate for each respective breed. During the weaning phase MR was gradually reduced over a 14-day (d) period (d −13 to d 0). Calves were blood sampled on d −14, −6, −3, 0, 1, 3, 8 and 14 relative to weaning (d 0) for subsequent haematological analysis. On d −14, 1 and 8, a subset of eight Holstein-Friesian calves randomly selected from the medium nutrition treatment and eight Jersey calves randomly selected from the high nutrition treatment, were blood sampled for gene expression profiling, targeting biomarkers of weaning stress. These two treatment groups were chosen to examine the effect of breed on expression of the genes of interest, as energy intake and animal performance were similar. There was no effect of breed × plane of nutrition interaction nor effect of plane of nutrition on any variable measured ( P > 0.05). Gradual weaning produced differential biological responses in the two breeds evidenced by breed × time interactions for lymphocyte, monocyte and red blood cell number, plasma haemoglobin and haptoglobin concentrations ( P < 0.05). The typical stress response consisting of neutrophilia and lymphopaenia was not observed for any treatment. An immune response to gradual weaning was observed as the relative gene expression level of the pro-apoptotic gene, Fas, increased on d 1 relative to d −14 ( P < 0.05). Relative gene expression levels were greater in Jersey calves compared with Holstein-Friesian for the pro-inflammatory cytokine CXCL8 ( P = 0.05) and the glucocorticoid receptor, GRα ( P < 0.05). The increased levels of these transcripts suggest that Jersey calves may have a more sensitive immune system compared with Holstein-Friesian.

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Section: Figurementioning

confidence: 99%

Characterisation of haematological profiles and whole blood relative gene expression levels in Holstein-Friesian and Jersey bull calves undergoing gradual weaning

Johnston

Kenny

Kelly

et al. 2016

animal

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“…In addition, point mutations for GR residues shown to be post-translationally modifi ed would be informative as to the role of these post-translational modifi cations in vivo. In addition, there are a number of additional polymorphisms in GR that have been linked to human disease states including metabolic syndrome and depression [ 78 ] which could be informative in the function of GR in vivo. Finally, the ease of using CRISPRs to generate targeted germ line mutations could be the solution to a problem that has existed in the fi eld of transcriptional regulation.…”

Section: Version 50: the Future Of Mice With Altered Gr Signalingmentioning

confidence: 99%

Animal Models of Altered Glucocorticoid Signaling

Harris

2015

Advances in Experimental Medicine and Biology

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In this chapter we will review genetically engineered mice with alterations in glucocorticoid signaling. Most of the mice involve direct alterations to the glucocorticoid receptor locus, but we will touch briefly on other relevant models including 11-β-HSD transgenics which alter tissue levels of ligand as well as mice with glucocorticoid excess. Of course, the number of mice with mutations in genes such as GR targets and transcriptional coregulators is beyond the scope of this chapter.

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“…The N363S polymorphism, originally rs6195, currently listed in dbSNP as rs56149945, results in an asparagine (N) to serine (S) change in amino acid in codon 363. The N363S polymorphism may infl uence the interaction of the GR with coactivators and/or corepressors, one of the known functions of the N-terminal domain of this receptor [ 76 ]. Only few reports have studied the role of this polymorphism in the response to exogenous GCs.…”

Section: Gr Gene Polymorphismsmentioning

confidence: 99%

Glucocorticoids in Pediatric Gastrointestinal Disorders

Iudicibus

Martelossi

Decorti

2015

Systemic Corticosteroids for Inflammatory Disorders in Pediatrics

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Pediatric Inflammatory Bowel Disease\ud Inflammatory bowel diseases (IBDs) are the most frequent chronic gastrointestinal disorders in pediatric age. They include two disease entities – Crohn’s disease (CD) and ulcerative colitis (UC) – which, although different in their pathogenesis, show common clinical characteristics such as chronic inflammation at different levels of the gastrointestinal tract and alternation between active and inactive phases. The incidence of IBD is increasing in recent years, particularly among children and adolescents, and it is currently estimated that 20–30 % of patients with IBD experience the onset of symptoms when they are under 20 years of age [1–3]. In childhood, IBDs are gener- ally more extended, more severe, and progress more rapidly than in adulthood. Moreover, therapy in children with IBD is more aggressive than in adults: Indeed, about 80 % of children need steroids, and about 30 % are subjected to an intestinal resection during a 5-year follow-up. Quality of life is severely affected in IBD, espe- cially for pediatric patients, owing to the chronic character of the disease that implies frequent hospitalizations and aggressive therapies, with a significant risk of side effects and a considerable impact on health care costs. IBD can result in loss of education and difficulty in gaining employment or insurance; overall, 15 % of patients with IBD are unable to work after 5–10 years of disease. Depressive disorders and low social func- tioning are also common among these patients, and the disease can also cause growth failure or retarded sexual development in young people [4–7]. It was recently reported that the mean individual annual costs in European countries amount to US$6,000 for CD and $4,600 for UC, and pediatric cases cost even more than adult ones [8]

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Glucocorticoid receptor polymorphisms and haplotypes and their expression in health and disease

Cited by 91 publications

References 106 publications

Characterisation of haematological profiles and whole blood relative gene expression levels in Holstein-Friesian and Jersey bull calves undergoing gradual weaning

Characterisation of haematological profiles and whole blood relative gene expression levels in Holstein-Friesian and Jersey bull calves undergoing gradual weaning

Animal Models of Altered Glucocorticoid Signaling

Glucocorticoids in Pediatric Gastrointestinal Disorders

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