Primary cortisol resistance: A familial syndrome and an animal model
| Autor: | Elizabeth O. Johnson, George R. Merriam, George P. Chrousos, A. C. M. Vingerhoeds, D. Lynn Loriaux, Brandon Dd, M. Tomita, Mortimer B. Lipsett |
|---|---|
| Rok vydání: | 1983 |
| Předmět: |
Adult
Male Primates Cortisol secretion Hypothalamo-Hypophyseal System endocrine system medicine.medical_specialty Cortisol awakening response Hydrocortisone medicine.drug_class Adrenal Gland Diseases Drug Resistance Pituitary-Adrenal System Biology Biochemistry Dexamethasone chemistry.chemical_compound Receptors Glucocorticoid Endocrinology Glucocorticoid receptor Reference Values Corticosterone Internal medicine medicine Animals Humans Receptor Skin Middle Aged Androgen Biological Evolution Pedigree Disease Models Animal chemistry Mineralocorticoid Female Steroids hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Journal of Steroid Biochemistry. 19:567-575 |
| ISSN: | 0022-4731 |
| Popis: | Primary cortisol resistance in man is a familial disease. It is characterized by increased plasma cortisol concentrations, high urinary free cortisol excretion, a normal circadian pattern of cortisol secretion, resistance to adrenal suppression by dexamethasone and absence of clinical stigmata of Cushing's syndrome. In its severe form, hypertension and hypokalemic alkalosis are present, owing to increased secretion of the sodium-retaining corticoids, corticosterone and deoxycorticosterone. In subjects with a less severe resistance to cortisol, there are no clinical abnormalities and the disease is revealed only by detailed examination of several parameters of cortisol metabolism. In the whole-cell assay (peripheral mononuclear leukocytes or fibroblasts) the glucocorticoid receptor shows a low affinity for dexamethasone. The receptor may be unsaturable as suggested by decreased receptor concentrations in broken-cell systems. Thus, generalized target-tissue resistance to cortisol, including the pituitary gland and the hypothalamus, is accompanied by a decreased negative feedback of the cortisol-ACTH feedback system resulting in increased ACTH secretion. This causes higher plasma cortisol to compensate for the end-organ resistance and also increases the production of adrenal mineralocorticoids, as by-products. Thus hypertension and hypokalemic alkalosis depends on the degree of the resistance. Cortisol resistance in many New World primate species is characterized by greatly increased plasma cortisol concentrations, decreased cortisol binding globulin capacity and affinity, high levels of plasma and urinary free cortisol, marked resistance of ACTH suppression by dexamethasone, and no physiologic evidence of glucocorticoid hormone excess. Target tissues have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. The New World primates, unlike man, have compensated for this cortisol resistance with intra-adrenal adaptations over the 50 million years of their evolutionary development. These primates also have abnormalities of other steroid hormone-receptor systems such as progesterone, estrogen, androgen and mineralocorticoid. In contrast, the human syndrome appears to be a recent mutation with pathophysiologic consequences. |
| Databáze: | OpenAIRE |
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