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MCF

Primary generalized glucocorticoid resistance

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Eur J Clin Invest. 2010 Jul 23. [Epub ahead of print]

Chrousos syndrome: a seminal report, a phylogenetic enigma and the clinical implications of glucocorticoid signalling changes.

Charmandari E, Kino T.

 

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

Abstract

Eur J Clin Invest 2010 Abstract Background Glucocorticoids regulate a broad spectrum of physiologic functions and play important roles in resting and stress homeostasis. Their actions are mediated by the nuclear glucocorticoid receptor (GR). Design Using a patient as a stimulus, we reviewed briefly the area of Primary Generalized Glucocorticoid Resistance in man and nonhuman primates. Results In man, Primary Generalized Glucocorticoid Resistance is a rare sporadic or familial syndrome characterized by target-tissue insensitivity to glucocorticoids and compensatory elevations in adrenocorticotropic hormone (ACTH), leading to increased secretion of cortisol and adrenal steroids with mineralocorticoid and/or androgenic activity, and causing hypermineralocorticoidism and hyperandrogenism without Cushing stigmata. The presentation, diagnosis and therapy of this condition are summarized. Many or, most likely, all New World primates have markedly elevated cortisol and ACTH, and resistance to dexamethasone suppression, without any pathology. These primates in fact have 'pan-steroid/sterol' resistance, including all five steroid hormones and 1,25-dihydroxy-vitamin D. In humans, the molecular basis of Primary Generalized Glucocorticoid Resistance has been mainly ascribed to recent mutations in the GR gene, which impair glucocorticoid signal transduction. In contrast, in the primates, steroid/sterol signalling systems have adapted under yet unknown selective pressures or genetic drift over many million years. Of course, other molecules of the signaling pathways may also be involved in both states. There are now a host of human states associated with tissue-specific pathologic glucocorticoid target tissue changes. These include allergic, autoimmune, inflammatory and lymphoproliferative disorders. Conclusions In recognition of Professor George P. Chrousos' extensive ground-breaking research in this field, and for the sake of brevity, we propose that 'Chrousos syndrome' is used instead of 'Primary Generalized Familial or Sporadic Glucocorticoid Resistance'.

 

PMID: 20649902 [PubMed - as supplied by publisher]

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