The Glucocorticoid Receptor and RU 486 in Man
Abstract
RU 486 is a prototype glucocorticoid antagonist with strong antiglucocorticoid activity in vitro and in vivo. Studies of its molecular mechanism of action have provided invaluable insights in the complex activation cascade of the GR itself. RU 486 effectively antagonizes glucocorticoids in most glucocorticoid-sensitive systems. Agonist effects, however, have been observed in some in vitro and in vivo systems, but remain the exception. In humans, administration of RU 486 causes generalized glucocorticoid resistance with high levels of cortisol compensating for the peripheral receptor blockade. This state is similar to that of patients with generalized familial glucocorticoid resistance. Because of its HPA axis stimulatory effects, RU 486 has limited chronic utility as an antiglucocorticoid. To date, the application of RU 486 can only be recommended in inoperable patients with ectopic ACTH secretion or adrenal carcinoma who have failed to respond to other treatments. The unusually long half-life of this drug also poses problems with titrating its dose within a therapeutic range. The development of a short-acting, selective glucocorticoid antagonist is therefore, a desirable goal of future research.
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Psoriatic patients have lower saliva cortisol levels.
“Psoriatic patients have lower saliva cortisol levels [138].”
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Yang-Yen, H.-F., Chambard, J.-C., Sun, Y.-L., Smeal, T., Schmidt, T. J., Drouin, J., & Karin, M. (1990) · Cell · doi:10.1016/0092-8674(90)90396-v · Cited by 1,553 · see citing works
Hurley, D. M., Accili, D., Stratakis, C. A., Karl, M., Vamvakopoulos, N., Rorer, E., Constantine, K., Taylor, S. I., & Chrousos, G. P. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115046 · Cited by 370 · see citing works
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Steroidogenesis in the skin: Implications for local immune functions
Slominski, A., Zbytek, B., Nikolakis, G., Manna, P. R., Skobowiat, C., Zmijewski, M., Li, W., Janjetovic, Z., Postlethwaite, A., Zouboulis, C. C., et al. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.02.006 · Cited by 369 · see citing works
Ramamoorthy, S., & Cidlowski, J. A. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01151-12 · Cited by 146 · see citing works
- Authors
- BAMBERGER, C. M., & CHROUSOS, G. P.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- BAMBERGER, CHRISTOPH M.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 1995-06
- Volume
- 761
- Issue
- 1
- Pages
- 296-310
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W1967716436
- Cited by
- 49
- References
- 3
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 3 · 2020: 1 · 2018: 2 · 2017: 1 · 2015: 1 · 2013: 3 · 2012: 1
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- RU486, mifepristone, glucocorticoid receptor, glucocorticoid antagonism, glucocorticoid resistance, cortisol, hypothalamic-pituitary-adrenal axis, ectopic ACTH secretion, adrenocortical carcinoma, elimination half-life
- MeSH terms
- Adrenocorticotropic Hormone, Cushing Syndrome, Drug Resistance, Female, Humans, Male, Models, Biological, Receptors, Glucocorticoid, Mifepristone, In Vitro Techniques
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