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11β‐Hydroxysteroid Dehydrogenases in the Brain
Author(s) -
HOLMES MEGAN C.,
YAU JOYCE L.W.,
KOTELEVTSEV YURI,
MULLINS JOHN J.,
SECKL JONATHAN R.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1286.035
Subject(s) - mineralocorticoid , glucocorticoid receptor , glucocorticoid , mineralocorticoid receptor , hydroxysteroid dehydrogenases , cortisone , biology , receptor , isozyme , gene , enzyme , intracellular , carbenoxolone , microbiology and biotechnology , endocrinology , biochemistry , dehydrogenase , gap junction
A bstract : Glucocorticoids affect a wide range of processes in the brain, altering neurotransmission, electrophysiological activity, metabolism, cell division, and death. These actions are mediated by corticosteroid receptors (glucocorticoid and mineralocorticoid) that modify transcriptional activity of target genes. The amount of steroid available to activate these receptors is not only dependent on the circulating levels but also on pre‐receptor metabolism of glucocorticoids occurring intracellularly. This metabolism is carried out by the enzymes 11β‐hydroxysteroid dehydrogenases (11β‐HSDs). There are two distinct isozymes, the products of distantly related genes. 11β‐HSD type 2 inactivates glucocorticoids to its inert 11‐keto derivative, while 11α‐HSD type 1 elevates intracellular glucocorticoid levels by regenerating active glucocorticoids from circulating 11‐dehydrocorticosterone or cortisone. This review highlights the important and very different roles the two enzymes play in the brain, outlining recent results obtained from studying mice with a targeted gene deletion in the 11β‐HSD1 or 11β‐HSD2 genes.