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This version published online on April 15, 2004
Molecular Endocrinology, doi:10.1210/me.2004-0005
A more recent version of this article appeared on July 1, 2004
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Submitted on January 5, 2004
Accepted on April 6, 2004

Corticosteroid Binding Globulin: A new target for cortisol driven obesity

Olga Ousova, Véronique Guyonnet-Duperat, Nathalie Iannuccelli, Jean-Pierre Bidanel, Denis Milan, Carine Genêt, Bastien Llamas, Martine Yerle, Joël Gellin, Patrick Chardon, Agnès Emptoz-Bonneton, Michel Pugeat, Pierre Mormède, and Marie-Pierre Moisan*

Laboratoire de Neurogénétique et Stress, INRA UMR1243-INSERM U471, Université Victor Segalen Bordeaux 2, Institut François Magendie, rue Camille Saint-Saëns, 33077 Bordeaux cédex, France; Laboratoire de Génétique Cellulaire, Centre de Recherche INRA de Toulouse-Auzeville, BP 27, 31326 Castanet Tolosan cédex France; Station de Génétique Quantitative et Appliquée, INRA, 78352 Jouy-en-Josas cédex France; Laboratoire d'Etude et de Recherche sur les Génomes, INRA, 78352 Jouy en Josas cédex, France; INSERM ERM 322, Hopital Debrousse, 29 rue Soeur Bouvier69322 Lyon cedex 05, France

* To whom correspondence should be addressed. E-mail: moisan{at}bordeaux.inserm.fr.

We present data suggesting that corticosteroid-binding globulin (CBG) may be the causal gene of a previously identified quantitative trait locus (QTL) associated with cortisol levels, fat and muscle content in a pig intercross. Because Cbg in human and mouse maps in the region orthologous to the pig region containing this QTL, we considered Cbg as an interesting positional candidate gene as CBG plays a major role in cortisol bioavailability. Firstly, we cloned pig Cbg from a BAC library and showed by fluorescent in situ hybridization (FISH) and radiation hybrid mapping that it maps on 7q26 at the peak of the QTL interval. Secondly, we detected in a subset of the pig intercross progeny a highly significant genetic linkage between CBG plasma binding capacity values and the chromosome 7 markers flanking the cortisol-associated QTL. In this population, CBG capacity is correlated positively to fat and negatively to muscle content. Thirdly, CBG capacity was 3 time higher in Meishan compared with Large White parental breeds and a seven-fold difference was found in Cbg mRNA expression between the two breeds. Overall, the data accumulated in this study point to Cbg gene as a key regulator of cortisol levels and obesity susceptibility.
Key words: Corticosteroid binding globulin • cortisol • obesity • genetics

NURSA Molecule Pages Link:

Ligands:   Hydrocortisone



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