Recent Advances in the Molecular Mechanisms Determining Tissue Sensitivity to Glucocorticoids: Novel Mutations, Circadian Rhythm, and Ligand-Induced Repression of the Human Glucocorticoid Receptor

August 2014 in “ BMC Endocrine Disorders ”

Nicolas C. Nicolaides, Evangelia Charmandari, George P. Chrousos, Tomoshige Kino

glucocorticoids human glucocorticoid receptor hGR Chrousos syndrome cortisol circadian rhythm CLOCK protein CRY proteins glucocorticoid-responsive genes glucocorticoid receptor

Studysummary This review summarizes the recent advances in molecular mechanisms influencing tissue sensitivity to glucocorticoids, emphasizing novel mutations and new information on the glucocorticoid receptor's circadian rhythm and ligand-induced repression, but reports no new results.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

The document reviews the molecular mechanisms affecting tissue sensitivity to glucocorticoids, focusing on novel mutations, circadian rhythm, and ligand-induced repression of the human glucocorticoid receptor (hGR). It explains how natural mutations in the hGR gene can lead to conditions like Chrousos syndrome, which causes insensitivity to glucocorticoids. The review also describes how the circadian rhythm, regulated by the central clock system in the hypothalamus, influences cortisol secretion and tissue sensitivity to glucocorticoids, with sensitivity being higher in the evening. It discusses the role of CLOCK protein in suppressing hGR activity through acetylation, and how CRY proteins can inhibit hGR transactivation of glucocorticoid-responsive genes. The document suggests that understanding these mechanisms could help develop new glucocorticoid compounds with selective activities and fewer side effects. It does not include a clinical trial or the number of people in a study.

View this study on bmcendocrdisord.biomedcentral.com →

Discuss this study in the Community →

Research cited in this study

3 / 3 results

research Primary Generalized Glucocorticoid Resistance And Hypersensitivity

48 citations , January 2011 in “Hormone Research in Paediatrics”

This review discusses the molecular basis and clinical implications of primary generalized glucocorticoid resistance and hypersensitivity, attributing them to mutations in the human glucocorticoid receptor gene, and reports no new clinical findings.

A Novel Point Mutation in the Ligand-Binding Domain of the Human Glucocorticoid Receptor Causing Generalized Glucocorticoid Resistance: The Importance of the C Terminus in Conferring Transactivational Activity

research A Novel Point Mutation in the Ligand-Binding Domain of the Human Glucocorticoid Receptor Causing Generalized Glucocorticoid Resistance: The Importance of the C Terminus in Conferring Transactivational Activity

91 citations , May 2005 in “The Journal of Clinical Endocrinology & Metabolism”

In this study, a novel mutation in the glucocorticoid receptor gene was identified in a young woman, impairing glucocorticoid signaling and leading to generalized glucocorticoid resistance.

research Female Pseudohermaphroditism Caused by a Novel Homozygous Missense Mutation of the GR Gene

94 citations , April 2002 in “The Journal of clinical endocrinology and metabolism/Journal of clinical endocrinology & metabolism”

This study describes the first case of female pseudohermaphroditism due to a novel homozygous glucocorticoid receptor gene mutation, indicating possible pre- and postnatal virilization in affected females.