Glucocorticoid resistance in humans and nonhuman primates

D. D. Brandon, A. J. Markwick, G. P. Chrousos, Donald (Lynn) Loriaux

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

In humans, the syndrome of cortisol resistance is characterized by the absence of signs and symptoms of Cushing's syndrome, elevated total and unbound plasma cortisol concentrations, and increases in urinary free cortisol excretion and plasma adrenocorticotropic hormone. In one family, a severely affected member had hypertension and hypokalemic alkalosis associated with increased plasma concentrations of corticosterone and deoxycorticosterone. These patients are resistant to suppression of the pituitary-adrenal axis by dexamethasone. Dexamethasone therapy, however, effectively corrected hypertension and hypokalemic alkalosis in the severely affected patient, without causing signs of glucocorticoid excess. The glucocorticoid receptor from these patients has a low affinity for glucocorticoids and is unstable during thermal activation. Both the molecular weight of the glucocorticoid receptor and the size of the corresponding mRNA are similar to those of normal controls. Transformation of B-lymphocytes with Epstein-Barr virus leads to induction of glucocorticoid receptors. Receptor induction, however, is lower in patient cells than those obtained from normal controls. This decreased induction parallels decreased expression of glucocorticoid receptor mRNA. Thus, in this form of glucocorticoid resistance the glucocorticoid receptor is abnormal and leads to diminished target organ responsiveness. Many New World primates exhibit glucocorticoid 'resistance', without apparent pathology. These species have markedly elevated plasma cortisol, both total and unbound concentrations, increased urinary free cortisol excretion, and marked increases in plasma adrenocorticotropic hormone and β-endorphin. The glucocorticoid receptors of these primates have decreased affinity for glucocorticoids, are thermolabile, and are not induced by Epstein-Barr virus transformation as indicated by specific binding and mRNA expression. Both the molecular weight of the glucocorticoid receptor and the size of the corresponding mRNA are similar to those of normal controls. Despite the high plasma cortisol concentrations in these primates, there is no sodium retention and aldosterone levels are actually increased. The kidney aldosterone receptor cross-reacts poorly with cortisol, explaining the absence of sodium retention. New World primates also have progesterone, estrogen, aldosterone, and vitamin D insensitivity, suggesting a common factor linking steroid hormone receptors.

Original languageEnglish (US)
JournalCancer Research
Volume49
Issue number8 SUPPL.
StatePublished - 1989
Externally publishedYes

Fingerprint

Glucocorticoid Receptors
Primates
Hydrocortisone
Glucocorticoids
Alkalosis
Messenger RNA
Aldosterone
Human Herpesvirus 4
Adrenocorticotropic Hormone
Dexamethasone
Molecular Weight
Sodium
Hypertension
Endorphins
Mineralocorticoid Receptors
Desoxycorticosterone
Cushing Syndrome
Steroid Receptors
Corticosterone
Glucocorticoid Receptor Deficiency

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Brandon, D. D., Markwick, A. J., Chrousos, G. P., & Loriaux, D. L. (1989). Glucocorticoid resistance in humans and nonhuman primates. Cancer Research, 49(8 SUPPL.).

Glucocorticoid resistance in humans and nonhuman primates. / Brandon, D. D.; Markwick, A. J.; Chrousos, G. P.; Loriaux, Donald (Lynn).

In: Cancer Research, Vol. 49, No. 8 SUPPL., 1989.

Research output: Contribution to journalArticle

Brandon, DD, Markwick, AJ, Chrousos, GP & Loriaux, DL 1989, 'Glucocorticoid resistance in humans and nonhuman primates', Cancer Research, vol. 49, no. 8 SUPPL..
Brandon DD, Markwick AJ, Chrousos GP, Loriaux DL. Glucocorticoid resistance in humans and nonhuman primates. Cancer Research. 1989;49(8 SUPPL.).
Brandon, D. D. ; Markwick, A. J. ; Chrousos, G. P. ; Loriaux, Donald (Lynn). / Glucocorticoid resistance in humans and nonhuman primates. In: Cancer Research. 1989 ; Vol. 49, No. 8 SUPPL.
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