Glucocorticoid Resistance

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


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.


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

List of Abbreviations


Adrenocorticotropic hormone


Activator protein-1


Arginine vasopressin


Cytosine-guanine dinucleotides


Corticotropin-releasing hormone






Glucocorticoid receptor


Glucocorticoid response elements


Glucocorticoid receptor-interacting protein 1




Human glucocorticoid receptor


Human glucocorticoid receptor alpha


Human glucocorticoid receptor beta

HPA axis

Hypothalamic-pituitary-adrenal axis


Heat-shock proteins


Ligand-binding domain


Mitogen-activated protein kinase


Nuclear factor-κB


Primary generalized glucocorticoid resistance


Phosphatidylinositol 3-kinase


Signal transducers and activators of transcription


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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