The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity.
Glucocorticoid receptors (GR) and 3-O-methyl-D glucose (3-O-MG) transport were determined in mononuclear leukocytes (MNL) from 11 abdominal obese subjects, 10 pituitary-dependent Cushing's syndrome (Cushing's disease) and 10 healthy controls. Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer, MNL of abdominal obese subjects were found to have 4855 +/- 1389 sites/cell which was significantly lower (p < 0.05) than controls (6234 +/- 1568 sites/cell), although no significant difference was found in the mean serum cortisol level. Their mean Kd (affinity) was also significantly lower than that found in the healthy controls (obese Kd:2.92 +/- 0.84 nmol/l, control Kd: 4.55 +/- 0.67 nM, p < 0.05). On the other hand, the receptor characteristics in Cushing's disease patients were within the normal range. At the same time, 3-O-MG transport was determined in the same subjects. In Cushing's disease, 3-O-MG transport was within the normal range, whereas in abdominal obesity this value was significantly lower than the healthy controls (abdominal obese: 31.90 +/- 8.20; control: 46.26 +/- 12.91 fmol/10(6) cell, min, p < 0.05). We also found a positive correlation between 3-O-MG transport and GR binding capacity in abdominal subjects (r = 0.89, p < 0.001), however we did not find such a correlation in Cushing's disease (r = 0.60, p > 0.05). These results indicated that, in abdominal obesity, the GR binding capacity in MNL is influenced by the changes in glucose transport.
Güven
M
M
Department of Medical Biology, Cerrahpaşa Medical Faculty, Istanbul University, Turkey.
Hatemi
H
H
Taşan
E
E
Altuntaş
Y
Y
Ulutin
T
T
Tezcan
V
V
Kanigür-Sultuybek
G
G
D019325:3-O-Methylglucose / Q000378:metabolism*; D000328:Adult; D001667:Binding, Competitive; D001692:Biological Transport; D001824:Body Constitution; D003480:Cushing Syndrome / Q000097:blood; D003907:Dexamethasone / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D009765:Obesity / Q000097:blood*; D011965:Receptors, Glucocorticoid / Q000097:blood*; D014316:Tritium
D011965:Receptors, Glucocorticoid; D014316:Tritium; D019325:3-O-Methylglucose; D003907:Dexamethasone; D006854:Hydrocortisone