Islam A, Chen Y, Poth M, Smith Z P, Deuster P A
Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Exp Clin Endocrinol Diabetes. 2012 Sep;120(8):477-81. doi: 10.1055/s-0032-1321809. Epub 2012 Jul 31.
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.
下丘脑 - 垂体 - 肾上腺轴的激活会导致皮质醇分泌，皮质醇与外周糖皮质激素受体结合，并介导一系列复杂的代谢和免疫效应。皮质醇还会与下丘脑和垂体中的受体结合，抑制促肾上腺皮质激素的进一步分泌，从而防止过度反应。在库欣病、肾上腺腺瘤/癌以及糖皮质激素抵抗中可出现糖皮质激素作用过度的情况。在这类病理状态下，存在糖皮质激素作用过度带来的健康后果，包括肥胖、高血压以及葡萄糖不耐受或糖尿病。我们推测，在外周组织中糖皮质激素受体增加可能在皮质醇分泌未增加的情况下介导糖皮质激素作用过度。本研究的目的是在白种人和非裔美国人样本中，研究白细胞中糖皮质激素受体密度与肥胖和糖尿病相关健康风险指标之间的关系。对糖皮质激素受体浓度与受试者体重指数、体脂百分比、腰围、胰岛素抵抗、血浆皮质醇水平、性别和血脂谱进行了比较。糖皮质激素受体密度增加与体重指数、体脂百分比、腰围和胰岛素抵抗显著相关。未观察到糖皮质激素受体密度与血脂谱之间存在显著相关性。此外，在白种人和非裔美国人受试者或男性和女性参与者之间，糖皮质激素受体密度未观察到显著差异。我们的结果表明，肥胖和2型糖尿病等高风险健康状况可能与一种下丘脑 - 垂体 - 肾上腺轴功能障碍形式有关，其特征是局部白细胞糖皮质激素受体过度表达。
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