Increased glucocorticoid receptor expression in human skeletal muscle cells may contribute to the pathogenesis of the metabolic syndrome.

Altered glucocorticoid hormone action may contribute to the etiology of the metabolic syndrome, but the molecular mechanisms are poorly defined. Tissue sensitivity to glucocorticoid is regulated by expression of the glucocorticoid receptor (GR)-alpha and 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1)-mediated intracellular synthesis of active cortisol from inactive cortisone. We have analyzed GRalpha and 11beta-HSD1 expression in skeletal myoblasts from men (n = 14) with contrasting levels of insulin sensitivity (euglycemic clamp measurements of insulin-dependent glucose disposal rate), blood pressure, and adiposity.

Maternal undernutrition during early to midgestation programs tissue-specific alterations in the expression of the glucocorticoid receptor, 11beta-hydroxysteroid dehydrogenase isoforms, and type 1 angiotensin ii receptor in neonatal sheep.

We have investigated the effects of maternal nutrient restriction in the sheep during the period of rapid placental growth (i.e. 28-77 days gestation; term = 147 days) on feto-placental growth and expression of the glucocorticoid receptor (GR), types 1 and 2 11beta-hydroxysteroid dehydrogenase (11betaHSD1, 11betaHSD2), and types 1 and 2 angiotensin II receptor (AT1, AT2) in fetal and neonatal offspring.

The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero.

Potential mechanisms underlying prenatal programming of hypertension in adult life were investigated using a rat model in which maternal protein intake was restricted to 9% vs. 18% casein (control) during pregnancy. Maternal low protein (MLP) offspring exhibit glucocorticoid-dependent raised systolic blood pressure throughout life (20-30 mm Hg above the control).

Regulation of glucocorticoid receptor alpha and beta isoforms and type I 11beta-hydroxysteroid dehydrogenase expression in human skeletal muscle cells: a key role in the pathogenesis of insulin resistance?

Glucocorticoid excess frequently results in obesity, insulin resistance, glucose intolerance, and hypertension and may be the product of altered glucocorticoid hormone action. Tissue sensitivity to glucocorticoid is regulated by the expression of glucocorticoid receptor isoforms (GRalpha and GRbeta) and 11beta-hydroxysteroid dehydrogenase type I (11betaHSD1)-mediated intracellular synthesis of active cortisol from inactive cortisone. We have analyzed the expression of GRalpha, GRbeta, and 11betaHSD1 and their hormonal regulation in skeletal myoblasts from men (n = 14) with contrasting levels of adiposity and insulin resistance.

Elevated plasma cortisol in glucose-intolerant men: differences in responses to glucose and habituation to venepuncture.

Recent evidence suggests that variations in cortisol activity within the physiological range contribute to associations between multiple cardiovascular risk factors. Plasma cortisol measurements during a glucose tolerance test differ in men with hypertension, insulin resistance, and glucose intolerance, but it is unclear whether this reflects altered responses of cortisol to glucose, altered circadian rhythm, or altered habituation to multiple sampling. We performed a single-blind randomized cross-over study comparing 75 g oral glucose with placebo in 39 fasted men (22 glucose intolerant and 17 controls) aged 68-77 yr.