Recent advances in the molecular mechanisms causing primary generalized glucocorticoid resistance

Nicolas C. Nicolaides, Agaristi Lamprokostopoulou, Amalia Sertedaki, Evangelia Charmandari

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Primary Generalized Glucocorticoid Resistance is a rare condition characterized by generalized, partial, target tissue insensitivity to glucocorticoids owing to inactivating mutations, insertions or deletions in the human glucocorticoid receptor (hGR) gene (NR3C1). Recent advances in molecular and structural biology have enabled us to elucidate the molecular mechanisms of action of the mutant receptors and to understand how certain conformational alterations …

Prevalence and cardiometabolic associations of the glucocorticoid receptor gene polymorphisms N363S and BclI in obese and non-obese black and white Mississippians

Eugen Melcescu, Michael Griswold, Lianbin Xiang, Sheila Belk, Denise Montgomery, Marilyn Bray, Kevin S. Del Ben, Gabriel I. Uwaifo, Gailen D. Marshall, Christian A. Koch

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OBJECTIVE: Polymorphisms (SNP) in the glucocorticoid receptor (GR) gene can alter sensitivity to glucocorticoids. Previous studies of the N363S and BclI SNP in the GR gene have shown a metabolic syndrome phenotype in mostly non-African populations. The obesity phenotype of African Americans …

The influence of combined oral contraceptives containing drospirenone on hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome

Djuro Macut, Ivana Božić Antić, Jelena Nestorov, Vladanka Topalović, Jelica Bjekić Macut, Dimitrios Panidis, Biljana Kastratović Kotlica, Efstathios Papadakis, Gordana Matić, Danijela Vojnović Milutinović

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OBJECTIVE: Most women with PCOS have increased adrenal androgen production, enhanced peripheral metabolism of cortisol and elevation in urinary excretion of its metabolites. Increased cortisol clearance in PCOS is followed by a compensatory overdrive of the hypothalamic-pituitary-adrenocortical (HPA) axis …

Novel insights into the molecular mechanisms underlying generalized glucocorticoid resistance and hypersensitivity syndromes

Nicolas C. Nicolaides, Evangelia Charmandari

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Glucocorticoids play a fundamental role in many physiologic functions and contribute substantially to the achievement of homeostasis. These pleiotropic glucocorticoid actions are mediated by a ubiquitously expressed transcription factor, the human glucocorticoid receptor (hGR), which may influence the transcription …