Publications by authors named "Charlotte Bruley"

2 Publications

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A novel promoter for the 11beta-hydroxysteroid dehydrogenase type 1 gene is active in lung and is C/EBPalpha independent.

Endocrinology 2006 Jun 16;147(6):2879-85. Epub 2006 Mar 16.

Endocrinology Unit, Centre for Cardiovascular Sciences, Queen's Institute for Medical Research, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, United Kingdom.

11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) increases intracellular glucocorticoid action by converting inactive to active glucocorticoids (cortisol, corticosterone) within cells. It is highly expressed in glucocorticoid target tissues including liver and lung, and at modest levels in adipose tissue and brain. A selective increase in adipose 11beta-HSD1 expression occurs in obese humans and rodents and is likely to be of pathogenic importance in the metabolic syndrome. Here we have used 5' rapid amplificaiton of cDNA ends (RACE) to identify a novel promoter, P1, of the gene encoding 11beta-HSD1. P1 is located 23 kb 5' to the previously described promoter, P2. Both promoters are active in liver, lung, adipose tissue, and brain. However, P1 (encoding exon 1A) predominates in lung and P2 (encoding exon 1B) predominates in liver, adipose tissue, and brain. Adipose tissue of obese leptin-deficient C57BL/6J-Lepob mice showed higher expression only of the P2-associated exon 1B-containing 11beta-HSD1 mRNA variant. In contrast to P2, which is CAAAT/enhancer binding protein (C/EBP)-alpha inducible in transiently transfected cells, the P1 promoter was unaffected by C/EBPalpha in transfected cells. Consistent with these findings, mice lacking C/EBPalpha had normal 11beta-HSD1 mRNA levels in lung but showed a dramatic reduction in levels of 11beta-HSD1 mRNA in liver and brown adipose tissue. These results therefore demonstrate tissue-specific differential regulation of 11beta-HSD1 mRNA through alternate promoter usage and suggest that increased adipose 11beta-HSD1 expression in obesity is due to a selective increase in activity of the C/EBPalpha-regulated P2 promoter.
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http://dx.doi.org/10.1210/en.2005-1621DOI Listing
June 2006

Growth selection in mice reveals conserved and redundant expression patterns of the insulin-like growth factor system.

Gen Comp Endocrinol 2004 Apr;136(2):248-59

Lehrstuhl für Molekulare Tierzucht und Biotechnologie/Genzentrum, Ludwig-Maximilians-Universität, 81377 Munich, Germany.

Transgenic and knockout models have been used successfully in order to attribute specific functions to distinct growth factors. However, it is not clear which from the different IGF-components are actually altered when growth is affected. Furthermore it is not clear if unique or redundant patterns of IGF-component expression are present under conditions of elevated or reduced growth. To address these questions we have used a unique set of mouse models generated by divergent selection for high and low body growth. The set of mouse models consisted of eight mouse lines established in different laboratories. We have studied systemic and local expression of growth relevant genes in these mouse lines highly diverging for body and carcass weights but also for nose-rump lengths. As a strictly conserved pattern, serum IGF-I levels were dramatically increased in all H-lines if compared with the respective L-lines. By contrast serum IGFBP concentrations did not reveal clear patterns of expression in response to growth selection: IGFBP-3 was elevated in some H-lines, IGFBP-2 was increased in H- or L-lines and IGFBP-4 was similar in H- and L-lines. The fact that IGFBP-2 was the only IGFBP elevated in part of the L-lines, identifies IGFBP-2 as an exclusive although facultative negative effector for growth in the circulation among all other IGFBPs. In muscle tissue from selected breeding groups characterized by specific increases of the carcass weights we found redundant patterns of gene expression indicating the absence of tissue-specific or uniquely fixed expression patterns during growth selection within muscle tissue. The finding that serum but not tissue IGF-I levels were strictly positively correlated with growth during growth selection argues for an important role of endocrine IGF-I for postnatal growth in mice.
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http://dx.doi.org/10.1016/j.ygcen.2003.12.019DOI Listing
April 2004