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- aggregation classification "A1".
- aggregation creator B419466.
- aggregation creator B419467.
- aggregation creator person.
- aggregation creator person.
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- aggregation creator person.
- aggregation date "2010".
- aggregation format "application/pdf".
- aggregation hasFormat 1060168.bibtex.
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- aggregation isPartOf urn:issn:0021-9258.
- aggregation language "eng".
- aggregation rights "I have transferred the copyright for this publication to the publisher".
- aggregation subject "Biology and Life Sciences".
- aggregation title "Increased glucocorticoid receptor expression and activity mediate the LPS resistance of SPRET/EI mice".
- aggregation abstract "SPRET/Ei mice are extremely resistant to acute LPS-induced lethal inflammation when compared to C57BL/6. We found that in vivo SPRET/Ei mice exhibit strongly reduced expression levels of cytokines and chemokines. To investigate the role of the potent antiinflammatory glucocorticoid receptor (GR) in the SPRET/Ei phenotype, mice were treated with the GR antagonist RU486 or bilateral adrenalectomy. Under such conditions, both C57BL/6 and SPRET/Ei mice were strongly sensitized to LPS and the differences in LPS response between SPRET/Ei and C57BL/6 mice were completely gone. These results underscore the central role of GR in the LPS hyporesponsiveness of SPRET/Ei mice. Compared to C57BL/6, SPRET/Ei mice were found to express higher GR levels, which were reflected in increased GR transactivation. Using a backcross mapping strategy, we demonstrate that the high GR transcription levels are linked to the Nr3c1 (GR) locus on chromosome 18 itself. Unexpectedly, SPRET/Ei mice exhibit a basal overactivation of the hypothalamic-pituitary-adrenal axis, namely strongly increased corticosterone levels, ACTH levels and adrenocortical size. As a consequence of the excess of circulating glucocorticoids (GCs), levels of hepatic gluconeogenic enzymes are increased and insulin secretion from pancreatic β-cells is impaired, both of which result in hyperglycemia and glucose intolerance in SPRET/Ei mice. We conclude that SPRET/Ei mice are unique since they display an unusual combination of elevated GR expression and increased endogenous GC levels. Hence, these mice provide a new and powerful tool for the study of GR- and GC-mediated mechanisms, including immune repressive functions, neuroendocrine regulation, insulin secretion, and carbohydrate metabolism.".
- aggregation authorList BK740751.
- aggregation endPage "31086".
- aggregation issue "40".
- aggregation startPage "31073".
- aggregation volume "285".
- aggregation aggregates 2937526.
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- aggregation isDescribedBy 1060168.
- aggregation similarTo jbc.M110.154484.
- aggregation similarTo LU-1060168.