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Glucocorticoid Resistance

  • Nicolas C. NicolaidesEmail author
  • Evangelia Charmandari
Chapter
  • 207 Downloads
Part of the Experientia Supplementum book series (EXS, volume 111)

Abstract

Primary generalized glucocorticoid resistance or Chrousos syndrome is a rare disorder, which affects all tissues expressing the human glucocorticoid receptor. It is characterized by generalized, partial tissue insensitivity to glucocorticoids caused by genetic defects in the NR3C1 gene. We and others have applied standard methods of molecular and structural biology to investigate the molecular mechanisms and conformational alterations through which the mutant glucocorticoid receptors lead to the broad spectrum of clinical manifestations of Chrousos syndrome. The ever-increasing application of novel technologies, including the next-generation sequencing, will enhance our knowledge in factors that influence the glucocorticoid signal transduction in a positive or negative fashion.

Keywords

Chrousos syndrome Glucocorticoid receptor Glucocorticoid signaling Glucocorticoids NR3C1 mutations Primary generalized glucocorticoid resistance 

List of Abbreviations

ACTH

Adrenocorticotropic hormone

AP-1

Activator protein-1

AVP

Arginine vasopressin

CpG

Cytosine-guanine dinucleotides

CRH

Corticotropin-releasing hormone

DHEA

Dehydroepiandrosterone

DHEAS

Dehydroepiandrosterone-sulfate

GR

Glucocorticoid receptor

GREs

Glucocorticoid response elements

GRIP1

Glucocorticoid receptor-interacting protein 1

GST

Glutathione-S-transferase

hGR

Human glucocorticoid receptor

hGRα

Human glucocorticoid receptor alpha

hGRβ

Human glucocorticoid receptor beta

HPA axis

Hypothalamic-pituitary-adrenal axis

HSP

Heat-shock proteins

LBD

Ligand-binding domain

MAPK

Mitogen-activated protein kinase

NF-κB

Nuclear factor-κB

PGGR

Primary generalized glucocorticoid resistance

PI3K

Phosphatidylinositol 3-kinase

STATs

Signal transducers and activators of transcription

UFC

Urinary free cortisol

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Nicolas C. Nicolaides
    • 1
    • 2
    Email author
  • Evangelia Charmandari
    • 1
    • 2
  1. 1.Division of Endocrinology, Metabolism and Diabetes, First Department of PediatricsNational and Kapodistrian University of Athens Medical School, “Aghia Sophia” Children’s HospitalAthensGreece
  2. 2.Division of Endocrinology and Metabolism, Center of Clinical, Experimental Surgery and Translational ResearchBiomedical Research Foundation of the Academy of AthensAthensGreece

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