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Glucocorticoid Resistance.

Nicolas C Nicolaides1,2, Evangelia Charmandari3,4

  • 1Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece. nnicolaides@bioacademy.gr.

Experientia Supplementum (2012)
|October 8, 2019
PubMed
Summary
This summary is machine-generated.

Primary generalized glucocorticoid resistance, or Chrousos syndrome, is a rare genetic disorder affecting glucocorticoid receptor function. Research investigates molecular mechanisms of NR3C1 gene defects causing tissue insensitivity to glucocorticoids.

Keywords:
Chrousos syndromeGlucocorticoid receptorGlucocorticoid signalingGlucocorticoidsNR3C1 mutationsPrimary generalized glucocorticoid resistance

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Primary generalized glucocorticoid resistance (Chrousos syndrome) is a rare disorder.
  • It affects all tissues expressing the human glucocorticoid receptor (GR).
  • Characterized by partial tissue insensitivity to glucocorticoids due to NR3C1 gene defects.

Purpose of the Study:

  • To investigate the molecular mechanisms and conformational alterations of mutant GRs.
  • To understand how these alterations lead to Chrousos syndrome manifestations.

Main Methods:

  • Standard methods of molecular and structural biology were applied.
  • Novel technologies, including next-generation sequencing, are being utilized.

Main Results:

  • Identified genetic defects in the NR3C1 gene cause generalized glucocorticoid insensitivity.
  • Molecular and structural biology studies reveal conformational changes in mutant GRs.

Conclusions:

  • Mutant glucocorticoid receptors due to NR3C1 gene defects underlie Chrousos syndrome.
  • Next-generation sequencing will advance understanding of glucocorticoid signal transduction factors.