Abstract
Activation of the hypothalamic-pituitary-adrenal axis leads to secretion of cortisol,
which binds to peripheral glucocorticoid receptor and mediates a complex series of
metabolic and immune effects. Cortisol also binds to receptors in the hypothalamus
and pituitary, and inhibits further secretion of adrenocorticotropic hormone thus
preventing an excessive response. Excess glucocorticoid effect is seen in Cushings
disease, adrenal adenomas/carcinomas and in glucocorticoid resistance. Within such
pathology there are health consequences of excessive glucocorticoid action, including
obesity, hypertension, and glucose intolerance or diabetes. We hypothesized that increased
glucocorticoid receptor in peripheral tissue might mediate an excess glucocorticoid
effect in the absence of increased cortisol secretion. The objective of the study
was to investigate the relationship between glucocorticoid receptor density in leukocytes
and health risk indices relevant to obesity and diabetes in a sample of Caucasian
and African American subjects. Comparison of glucocorticoid receptor concentration
with subject body mass index, percentage body fat, waist circumference, insulin resistance,
plasma cortisol levels, gender, and lipid profiles were conducted. Increased glucocorticoid
receptor density significantly correlated with body mass index, percentage body fat,
waist circumference, and insulin resistance. No significant correlation was observed
for glucocorticoid receptor density with lipid profiles. Furthermore, no significant
differences were observed in glucocorticoid receptor density between Caucasian and
African American subjects or male and female participants. Our results show that high
risk health conditions, such as obesity and type-2 diabetes, may be associated with
a form of hypothalamic-pituitary-adrenal axis dysfunction, characterized by localized
leukocyte glucocorticoid receptor over-expression.
Key words
glucocorticoid receptor - insulin resistance - leukocyte
