Cell- and tIssue-specific effects of corticosteroids in relation to glucocorticoid resistance: examples from the brain.
The biological mechanisms that determine cell-specific responses to glucocorticoid hormones may overlap with those that are associated with acquired glucocorticoid resistance. Cell and tIssue specificity can be brought about in many different ways. Studies on the brain, an important glucocorticoid target tIssue, may provide examples of regulatory mechanisms underlying response specificity at multiple levels. In this commentary a number of such mechanisms are discussed, with emphasis on regulation of glucocorticoid bio-availability by the efflux transporter P-glycoprotein and on the variable presence of nuclear proteins which modulate or interfere with gluco- and mineralocorticoid receptor-mediated transcription.
Meijer
O C
OC
Division of Medical Pharmacology, Leiden/Amsterdam Centre for Drug Research, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands. o.meijer@lacdr.leidenuniv.nl
Karssen
A M
AM
de Kloet
E R
ER
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001682:Biological Availability; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D019281:Dimerization; D004351:Drug Resistance; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid