11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response.
11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) interconverts inactive cortisone and active cortisol. Although bidirectional, in vivo it is believed to function as a reductase generating active glucocorticoid at a prereceptor level, enhancing glucocorticoid receptor activation. In this revi...
| Hoofdauteurs: | , , , , , , , |
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| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
2004
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| _version_ | 1826266523668316160 |
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| author | Tomlinson, J Walker, E Bujalska, I Draper, N Lavery, G Cooper, MS Hewison, M Stewart, P |
| author_facet | Tomlinson, J Walker, E Bujalska, I Draper, N Lavery, G Cooper, MS Hewison, M Stewart, P |
| author_sort | Tomlinson, J |
| collection | OXFORD |
| description | 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) interconverts inactive cortisone and active cortisol. Although bidirectional, in vivo it is believed to function as a reductase generating active glucocorticoid at a prereceptor level, enhancing glucocorticoid receptor activation. In this review, we discuss both the genetic and enzymatic characterization of 11beta-HSD1, as well as describing its role in physiology and pathology in a tissue-specific manner. The molecular basis of cortisone reductase deficiency, the putative "11beta-HSD1 knockout state" in humans, has been defined and is caused by intronic mutations in HSD11B1 that decrease gene transcription together with mutations in hexose-6-phosphate dehydrogenase, an endoluminal enzyme that provides reduced nicotinamide-adenine dinucleotide phosphate as cofactor to 11beta-HSD1 to permit reductase activity. We speculate that hexose-6-phosphate dehydrogenase activity and therefore reduced nicotinamide-adenine dinucleotide phosphate supply may be crucial in determining the directionality of 11beta-HSD1 activity. Therapeutic inhibition of 11beta-HSD1 reductase activity in patients with obesity and the metabolic syndrome, as well as in glaucoma and osteoporosis, remains an exciting prospect. |
| first_indexed | 2024-03-06T20:40:15Z |
| format | Journal article |
| id | oxford-uuid:340cf4d4-c4a9-437b-936d-919a5cc794bc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:40:15Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:340cf4d4-c4a9-437b-936d-919a5cc794bc2022-03-26T13:23:38Z11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:340cf4d4-c4a9-437b-936d-919a5cc794bcEnglishSymplectic Elements at Oxford2004Tomlinson, JWalker, EBujalska, IDraper, NLavery, GCooper, MSHewison, MStewart, P11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) interconverts inactive cortisone and active cortisol. Although bidirectional, in vivo it is believed to function as a reductase generating active glucocorticoid at a prereceptor level, enhancing glucocorticoid receptor activation. In this review, we discuss both the genetic and enzymatic characterization of 11beta-HSD1, as well as describing its role in physiology and pathology in a tissue-specific manner. The molecular basis of cortisone reductase deficiency, the putative "11beta-HSD1 knockout state" in humans, has been defined and is caused by intronic mutations in HSD11B1 that decrease gene transcription together with mutations in hexose-6-phosphate dehydrogenase, an endoluminal enzyme that provides reduced nicotinamide-adenine dinucleotide phosphate as cofactor to 11beta-HSD1 to permit reductase activity. We speculate that hexose-6-phosphate dehydrogenase activity and therefore reduced nicotinamide-adenine dinucleotide phosphate supply may be crucial in determining the directionality of 11beta-HSD1 activity. Therapeutic inhibition of 11beta-HSD1 reductase activity in patients with obesity and the metabolic syndrome, as well as in glaucoma and osteoporosis, remains an exciting prospect. |
| spellingShingle | Tomlinson, J Walker, E Bujalska, I Draper, N Lavery, G Cooper, MS Hewison, M Stewart, P 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. |
| title | 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. |
| title_full | 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. |
| title_fullStr | 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. |
| title_full_unstemmed | 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. |
| title_short | 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. |
| title_sort | 11beta hydroxysteroid dehydrogenase type 1 a tissue specific regulator of glucocorticoid response |
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