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Tissue glucocorticoid resistance/hypersensitivity syndromes.
Tomoshige Kino1, Massimo U De Martino, Evangelia Charmandari
1Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1583, USA. kinot@mail.nih.gov
The Journal of Steroid Biochemistry and Molecular Biology
|August 29, 2003
Summary
Tissue sensitivity to glucocorticoids can be altered, leading to resistance or hypersensitivity. This review examines glucocorticoid resistance syndrome and factors influencing glucocorticoid receptor activity in disease.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Glucocorticoids are vital for bodily functions and disease treatment.
- Altered tissue sensitivity to glucocorticoids, including resistance and hypersensitivity, impacts disease course and therapy.
- Glucocorticoid resistance syndrome (GRS) involves mutations in the glucocorticoid receptor (GR) gene.
Purpose of the Study:
- To review molecular analyses of familial/sporadic GRS cases.
- To discuss novel molecules influencing GR activity and glucocorticoid sensitivity in pathological conditions.
Main Methods:
- Review of molecular analyses from eight GRS cases (five familial, three sporadic).
- Discussion of potential roles for HIV-1 Vpr, Tat, FLASH, and COUP-TFII in GR regulation.
Main Results:
- Familial/sporadic GRS is linked to inactivating GR gene mutations, causing generalized insensitivity.
- Inflamed tissues in autoimmune/allergic diseases may exhibit glucocorticoid resistance.
- Glucocorticoid hypersensitivity is implicated in metabolic syndrome and HIV-1 infection.
Conclusions:
- Changes in tissue glucocorticoid sensitivity significantly affect disease pathogenesis and treatment.
- Novel molecules like HIV-1 Vpr, Tat, FLASH, and COUP-TFII may modulate GR activity and contribute to altered glucocorticoid sensitivity in disease.