Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51.

摘要: 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 squirrel monkey GR does not result from substitutions in the receptor, because expressed vitro exhibits Rather, express a soluble factor that, mixing studies cytosol lymphocytes (SML) and mouse L929 cells, by 11-fold. In an effort identify this factor, cellular levels components heterocomplex SML human (HL) were compared. immunophilin FKBP51 was 13-fold higher than HL cytosol; FKBP52 42% cytosol. A role changes immunophilins, causing resistance primates, is supported following: observed cells other resistance; elevated level reflected abundance heat shock protein 90 complexes SML; when cytosols mixed, decrease associated incorporation into heterocomplexes; effect on reproduced COS expressing FKBP51; both heterocomplexes blocked FK506. Regulation represents previously unrecognized mechanism regulating sensitivity.