Increased Glucocorticoid Activity in Men With Cardiovascular Risk Factors

Abstract

Abstract-The association between hypertension and insulin resistance might be explained by increased activity of the principal glucocorticoid, cortisol. Recent data show that the intensity of dermal vasoconstriction after topical application of glucocorticoids is increased in patients with essential hypertension. In this report, we examine whether increased glucocorticoid sensitivity or secretion is associated with insulin resistance and is a cause or consequence of hypertension. We studied 32 men (aged 47 to 56 years) from a cross-sectional study and 105 men (aged 23 to 33 years) in whom predisposition to high blood pressure has been defined by their own blood pressure and the blood pressures of their parents. In both populations, increased dermal glucocorticoid sensitivity was associated with relative hypertension, insulin resistance, and hyperglycemia. In young men with higher blood pressure whose parents also had high blood pressure, enhanced glucocorticoid sensitivity was accompanied by enhanced secretion of cortisol, enhanced ligand-binding affinities for dexamethasone in leukocytes, and impaired conversion of cortisol to inactive metabolites (cortisone and 5␤-dihydrocortisol). Increased tissue sensitivity to cortisol, amplified by enhanced secretion of cortisol, is a feature of the familial predisposition to high blood pressure rather than a secondary effect of high blood pressure. It may be mediated by an abnormal glucocorticoid receptor, and it may contribute to the association between hypertension and insulin resistance. (Hypertension. 1998;31:891-895.)Key Words: receptors, corticosteroid Ⅲ adrenal cortex hormones Ⅲ blood pressure Ⅲ insulin Ⅲ blood vessels M any patients with atheromatous disease have identifiable risk factors, including hypertension, insulin resistance, glucose intolerance, and central obesity. These risk factors often occur together, 1 but the reason for their association is not clear. The same list of abnormalities can be reproduced in Cushing's syndrome, caused by excessive activity of glucocorticoid hormones such as cortisol. In health, the activity of cortisol is determined by a combination of factors, including secretion rate from the adrenal, metabolic clearance rate, and tissue sensitivity. Recent studies suggest that these factors may be abnormal in patients with essential hypertension, in whom impaired metabolism of cortisol 2,3 is accompanied by increased sensitivity to glucocorticoids in the skin. 4 Similarly, in inbred rats with hypertension, glucocorticoid metabolism is impaired 5 and sensitivity of mesenteric vessels to dexamethasone is enhanced. 6 In addition, in rats and humans, polymorphisms of the glucocorticoid receptor gene have been linked with high blood pressure 7,8 and insulin resistance. The aims of the present studies were to establish whether abnormalities of glucocorticoid secretion, metabolism, or tissue sensitivity are (1) associated with hypertension, insulin resistance, glucose intolerance, and obesity and (2) likely to be a cause or consequence of hyp...

Glucocorticoids, metabolism and metabolic diseases

“…Notably, excessive GC levels as observed in Cushing's syndrome have been identified to be instrumental for the obesity in these patients [24]. Indeed, hyperactivity of the HPA axis is positively correlated with the Metabolic Syndrome as demonstrated in subjects with glucose intolerance, hypertension, and insulin resistance [32,34,161,162], suggesting a causative role for GCs in the obese phenotype. Consistently, treatment of obese rats with the GR antagonist RU486 or adrenalectomy reverse the obese phenotype in these animals [163,164].…”

11?-Hydroxysteroid dehydrogenase Type 1 in obesity and Type 2 diabetes

“…[59,60,61]) and might explain the association of low birth weight and insulin resistance [62]. Alterations in cortisol excretion and HPA axis regulation have specifically been observed in diabetes mellitus [63,64,65,66,67].…”

Possible Association of Heart Failure Status With Synthetic Balance Between Aldosterone and Dehydroepiandrosterone in Human Heart

“…35,36 The plasma levels of cortisol increase with aging, contrasting with those of DHEA. 35,36 It is still unclear whether cortisol or CYP11B1, the key enzyme catalyzing the final step in the synthesis of cortisol, is expressed in human heart. In the present analysis, we could not detect the expression of CYP11B1 by using RT-PCR followed by Southern blot analysis and real-time RT-PCR in human ventricles.…”