Corticosteroid receptors in mononuclear leucocytes of obese subjects.
Abnormalities of the hypothalamus-pituitary-adrenal axis and hypersensitivity to corticosteroids have been suggested as major determinants of the development of visceral obesity. Since at the cellular level most effects of corticosteroids are mediated by specific receptors, we evaluated the number of type I and type II corticosteroid receptors in mononuclear leucocytes of 26 obese and 13 control subjects. We also studied the relationship between corticosteroid receptors, measured by radioreceptor assay, and abdominal visceral fat, evaluated by computed tomography scan, plasma and urine corticosteroid hormone concentrations and overall glucose metabolism, assessed by euglycaemic-hyperinsulinaemic clamp. We observed a decrease in type II receptors in the obese subjects (1746 +/- 160 vs 2829 +/- 201 per cell; P < 0.0001), with no change in type I receptors. Type II receptors decreased in relation to body mass index (r = -0.53; P < 0.005) and total glucose disposal (r = 0.51; P < 0.01). Abdominal visceral fat did not correlate with type II receptor number, but did correlate with total glucose disposal (r = -0.35; P < 0.05); the rate of glucose disposal was lower in obese subjects (3.3 +/- 0.3 vs 7.4 +/- 0.4 mg/kg per min; P < 0.001). Plasma and urine cortisol did not differ between the two groups. However, a direct correlation between type II receptor number and both plasma (r = 0.43; P < 0.02) and urine cortisol concentrations (r = 0.60; P < 0.05) was observed. In conclusion, the number of type II corticosteroid receptors in mononuclear leucocytes was found to be lower in obese subjects. This abnormality appears to be related to the degree of adiposity and to the main endocrine-metabolic features of the obesity syndrome, further supporting the hypothesis of involvement of hypothalamus-pituitary-adrenal axis hyperactivity in the pathophysiology of obesity.
Vettor
R
R
Endocrine-Metabolic Laboratory, University of Padova, Italy.
Macor
C
C
Novo
F
F
Gottardo
C
C
Zovato
S
S
Simoncini
M
M
Federspil
G
G
Armanini
D
D
D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D001824:Body Constitution; D015992:Body Mass Index; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007328:Insulin / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D011869:Radioligand Assay; D011987:Receptors, Steroid / Q000032:analysis*; D012044:Regression Analysis; D014057:Tomography, X-Ray Computed
D001786:Blood Glucose; D007328:Insulin; D011987:Receptors, Steroid; D006854:Hydrocortisone