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Title: Tissue mRNA expression of the glucocorticoid receptor and its splice variants in fatal critical illness
Authors: Peeters, R P *
Hagendorf, A *
Vanhorebeek, Ilse
Visser, T J
Klootwijk, W
Mesotten, Dieter
Wouters, Pieter
Koper, J W
de Jong, F H
Feelders, R A
Lamberts, S W J
Van den Berghe, Greet # ×
Issue Date: Jul-2009
Publisher: Blackwell Scientific Publications
Series Title: Clinical Endocrinology vol:71 issue:1 pages:145-153
Abstract: BACKGROUND: Critical illness results in activation of the hypothalamic-pituitary-adrenal (HPA) axis, which might be accompanied by a peripheral adaptation in glucocorticoid sensitivity. Tissue sensitivity is determined by the active glucocorticoid receptor GRalpha, of which two splice variants involving the hormone-binding domain exist, GRbeta and GR-P. OBJECTIVE: To study tissue mRNA expression of the GR and its splice variants in fatal critical illness. DESIGN AND METHODS: We assessed mRNA expression of the GRalpha, GRbeta and GR-P variants in liver (n = 58) and muscle (n = 65) of patients who had died after intensive care, and had been randomized for insulin treatment. We analysed whether GR mRNA expression was associated with insulin treatment, cortisol levels and glucocorticoid treatment. RESULTS: GRalpha and GR-P mRNA constituted 87 +/- 8% and 13 +/- 2%, respectively, of total GR mRNA in liver. GRbeta mRNA could only be amplified in five liver samples. All variants were present in most muscle samples (alpha = 96 +/- 11%, P = 3.9 +/- 0.4%, beta = 0.010 +/- 0.002%). GR expression was not associated with insulin therapy. A strong positive relationship was observed between the different GR variants in both liver and muscle (P < 0.001 for all). Serum cortisol levels were negatively associated with liver GRalpha and muscle GR-P expression (P < 0.05). mRNA expression of both liver GRalpha and GR-P, but not muscle GR, was substantially lower in patients who had received exogenous glucocorticoids (P < 0.01). CONCLUSION: We demonstrate the presence of GRalpha and GR-P mRNA in liver and of GRalpha, GRbeta and GR-P mRNA in muscle, with no evidence for altered splicing in critical illness. In contrast to muscle GR, liver GR expression was substantially lower in patients receiving exogenous glucocorticoids.
URI: 
ISSN: 0300-0664
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Intensive Care Medicine (-)
Laboratory of Intensive Care Medicine
Unit for Clinical-Translational Research (-)
* (joint) first author
× corresponding author
# (joint) last author

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