Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism.
Interconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. The enzyme 11beta-HSD type 1 (11beta-HSD1) catalyzes...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1826288036127703040 |
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| author | Hult, M Elleby, B Shafqat, N Svensson, S Rane, A Jörnvall, H Abrahmsen, L Oppermann, U |
| author_facet | Hult, M Elleby, B Shafqat, N Svensson, S Rane, A Jörnvall, H Abrahmsen, L Oppermann, U |
| author_sort | Hult, M |
| collection | OXFORD |
| description | Interconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. The enzyme 11beta-HSD type 1 (11beta-HSD1) catalyzes the conversion of cortisone to its active receptor-binding derivative cortisol, whereas 11beta-HSD type 2 performs the reverse reaction. Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical application in insulin resistance and other metabolic disorders. We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. The enzyme, either as full-length, membrane-attached, or as a transmembrane domain-deleted, soluble form, mediates exclusively conversion between 7-ketocholesterol and 7beta-hydroxycholesterol with similar k(cat) values as observed with glucocorticoid hormones. Thus, human, rat, and mouse 11beta-HSD1 have dual enzyme activities like the recently described 7alpha-hydroxysteroid dehydrogenase/11beta-hydroxysteroid dehydrogenase from hamster liver, but differ fundamentally from the latter in that 7beta-OH rather than 7alpha-OH dehydrogenase constitutes the second activity. These results demonstrate an enzymatic origin of species differences in 7-oxysterol metabolism, establish the origin of endogenous 7beta-OH cholesterol in humans, and point to a possible involvement of 11beta-HSD1 in atherosclerosis. |
| first_indexed | 2024-03-07T02:07:39Z |
| format | Journal article |
| id | oxford-uuid:9f89b4aa-1cb4-4f3c-a454-d39cf9ec1145 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:07:39Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:9f89b4aa-1cb4-4f3c-a454-d39cf9ec11452022-03-27T00:58:39ZHuman and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9f89b4aa-1cb4-4f3c-a454-d39cf9ec1145EnglishSymplectic Elements at Oxford2004Hult, MElleby, BShafqat, NSvensson, SRane, AJörnvall, HAbrahmsen, LOppermann, UInterconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. The enzyme 11beta-HSD type 1 (11beta-HSD1) catalyzes the conversion of cortisone to its active receptor-binding derivative cortisol, whereas 11beta-HSD type 2 performs the reverse reaction. Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical application in insulin resistance and other metabolic disorders. We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. The enzyme, either as full-length, membrane-attached, or as a transmembrane domain-deleted, soluble form, mediates exclusively conversion between 7-ketocholesterol and 7beta-hydroxycholesterol with similar k(cat) values as observed with glucocorticoid hormones. Thus, human, rat, and mouse 11beta-HSD1 have dual enzyme activities like the recently described 7alpha-hydroxysteroid dehydrogenase/11beta-hydroxysteroid dehydrogenase from hamster liver, but differ fundamentally from the latter in that 7beta-OH rather than 7alpha-OH dehydrogenase constitutes the second activity. These results demonstrate an enzymatic origin of species differences in 7-oxysterol metabolism, establish the origin of endogenous 7beta-OH cholesterol in humans, and point to a possible involvement of 11beta-HSD1 in atherosclerosis. |
| spellingShingle | Hult, M Elleby, B Shafqat, N Svensson, S Rane, A Jörnvall, H Abrahmsen, L Oppermann, U Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. |
| title | Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. |
| title_full | Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. |
| title_fullStr | Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. |
| title_full_unstemmed | Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. |
| title_short | Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. |
| title_sort | human and rodent type 1 11beta hydroxysteroid dehydrogenases are 7beta hydroxycholesterol dehydrogenases involved in oxysterol metabolism |
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