Expression of the mRNAs coding for the glucocorticoid receptor isoforms in obesity.
OBJECTIVE
Glucocorticoids may be a pathophysiological mediator for the development of visceral obesity. In obese patients, adipose tissue reactivation of cortisone to cortisol is enhanced. In addition, changes in glucocorticoid receptor (GR) could also be important, either at the central nervous system level, by modulating the negative glucocorticoid feedback, or at a peripheral level, by regulating adipose tissue activity.


METHODS
Using quantitative reverse transcriptase-polymerase chain reaction, we studied the expression of the GR mRNA isoforms (active, GRalpha; inactive, GRbeta) in circulating mononuclear leukocytes (in which GR shares the same regulation with central nervous system GR) obtained from normal weight women (n = 65) and patients with gluteofemoral (n = 26) or visceral (n = 39) obesity. Using in situ hybridization, we measured GRalpha mRNA levels in adipose tissue from control (n = 10) or obese (n = 15) patients.


RESULTS
The mean alpha/beta ratio was decreased in mononuclear leukocytes from obese patients (2.6, 9.2, and 32.1, respectively). GRalpha mRNA levels were significantly decreased in subcutaneous abdominal adipose tissue obtained from obese patients compared with nonobese ones, suggesting the existence of a downregulation of GR gene expression. This phenomenon was not found in visceral adipose tissue.


CONCLUSIONS
This suggests that, in obese patients, the relative insensitivity to the negative glucocorticoid feedback is, at least in part, subsequent to a dysregulation of the GRalpha/GRbeta ratio and that visceral, but not subcutaneous, adipose tissue retains a full capacity to respond to increased local generation of cortisol.
Boullu-Ciocca
Sandrine
S
Service d'Endocrinologie and Centre d'Investigation Clinique, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
Paulmyer-Lacroix
Odile
O
Fina
Frédéric
F
Ouafik
L'Houcine
L
Alessi
Marie-Christine
MC
Oliver
Charles
C
Grino
Michel
M
D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D017403:In Situ Hybridization; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D020033:Protein Isoforms; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone