The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Glucocorticoid Resistance in the Squirrel Monkey Is Associated with Overexpression of the Immunophilin FKBP511
Abstract
Squirrel monkeys are neotropical primates that have high circulating cortisol to compensate for expression of glucocorticoid receptors (GRs) with reduced affinity. The low binding affinity of squirrel monkey GR does not result from substitutions in the receptor, because squirrel monkey GR expressed in vitro exhibits high affinity. Rather, squirrel monkeys express a soluble factor that, in mixing studies of cytosol from squirrel monkey lymphocytes (SML) and mouse L929 cells, reduced GR binding affinity by 11-fold. In an effort to identify this factor, the cellular levels of components of the GR heterocomplex in SML and human lymphocytes (HL) were compared. The immunophilin FKBP51 was 13-fold higher in SML than in HL cytosol; FKBP52 in SML was 42% of that in HL cytosol. A role for changes in immunophilins, causing glucocorticoid resistance in neotropical primates, is supported by the following: the changes in FKBP51 and FKBP52 were observed in cells from other neotropical primates with glucocorticoid resistance; the elevated level of FKBP51 was reflected in an abundance of FKBP51 in heat shock protein 90 complexes in SML; when cytosols of SML and L929 cells were mixed, the decrease in GR binding was associated with incorporation of FKBP51 into GR heterocomplexes; the effect of SML cytosol on GR binding was reproduced with cytosol from COS cells expressing squirrel monkey FKBP51; and both the effect of SML cytosol on GR binding and the incorporation of FKBP51 into GR heterocomplexes were blocked by FK506. Regulation of GR binding by FKBP51 represents a previously unrecognized mechanism for regulating glucocorticoid sensitivity.
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“Thus, the relative concentrations of FKBP51 and FKBP52 in the cell dictate the level of GR activity in vivo23,28,55.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [55]
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Abbott, D. H., Keverne, E. B., Bercovitch, F. B., Shively, C. A., Mendoza, S. P., Wendy Saltzman, A., Snowdon, C. T., Ziegler, T. E., Banjevic, M., Garland, T., et al. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(02)00037-5 · Cited by 748
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Metadata
- Authors
- Reynolds, P. D., Ruan, Y., Smith, D. F., & Scammell, J. G.
- Affiliations
- University of South Alabama (US)
- University of Nebraska Medical Center (US)
- Corresponding author
- Scammell, J. G.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1999-02
- Volume
- 84
- Issue
- 2
- Pages
- 663-669
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1978913374
- Cited by
- 184
- References
- 43
- Citations by year
- 2026: 1 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 8 · 2019: 5 · 2018: 2 · 2017: 7 · 2016: 7 · 2015: 6 · 2014: 6 · 2013: 7 · 2012: 11
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (01254, 13200)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-48218, R01DK048218)
- National Center for Research Resources (P40RR001254, R24RR013200)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- glucocorticoid resistance, squirrel monkey, FKBP51, FKBP52, immunophilins, glucocorticoid receptor, receptor binding affinity, HSP90, lymphocytes, Neotropical primates, cortisol, FK506
- MeSH terms
- Animals, Cytosol, Drug Resistance, Glucocorticoids, Humans, Immunosuppressive Agents, Lymphocytes, Receptors, Glucocorticoid, Saimiri, Gene Expression, Tacrolimus, HSP90 Heat-Shock Proteins, Immunophilins, Sirolimus, Tacrolimus Binding Proteins
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