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Glucocorticoid Resistance

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Genetics of Endocrine Diseases and Syndromes

Part of the book series: Experientia Supplementum ((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.

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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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Authors and Affiliations

  1. Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, “Aghia Sophia” Children’s Hospital, Athens, Greece

    Nicolas C. Nicolaides & Evangelia Charmandari

  2. Division of Endocrinology and Metabolism, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece

    Nicolas C. Nicolaides & Evangelia Charmandari

Authors
  1. Nicolas C. Nicolaides
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  2. Evangelia Charmandari
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Correspondence to Nicolas C. Nicolaides .

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Editors and Affiliations

  1. 2nd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

    Peter Igaz

  2. Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, “Lendület” Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary

    Attila Patócs

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Nicolaides, N.C., Charmandari, E. (2019). Glucocorticoid Resistance. In: Igaz, P., Patócs, A. (eds) Genetics of Endocrine Diseases and Syndromes. Experientia Supplementum, vol 111. Springer, Cham. https://doi.org/10.1007/978-3-030-25905-1_6

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