Characterization of 11β-HSD1B gene expression and enzymatic activity
Nuclease protection analysis has been used to study the distribution of an mRNA that has been predicted to give rise to a truncated form of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD1B). The 11β-HSD1B mRNA was found exclusively in the kidney, predominantly localized within the medulla with...
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Veröffentlicht in: | Molecular and cellular endocrinology 1993-04, Vol.92 (2), p.247-251 |
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description | Nuclease protection analysis has been used to study the distribution of an mRNA that has been predicted to give rise to a truncated form of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD1B). The 11β-HSD1B mRNA was found exclusively in the kidney, predominantly localized within the medulla with low amounts of the message in the cortex. Neither the renal papilla nor a range of peripheral and central tissues showed evidence of 11β-HSD1B mRNA. Expression of the whole (11β-HSD1A) and truncated enzymes in COS cells resulted in immunoreactive 34 kDa and 26 kDa proteins respectively, while kidney homogenates showed 34 kDa and 40 kDa species. The 11β-HSD1A enzyme converted corticosterone and cortisol to their respective 11-dehydro metabolites with an absolute dependence on NADP as co-factor, while the 26 kDa 11β-HSD1B protein was unable to metabolize either steroid. These results suggest that transcription of the 11β-HSD1B mRNA is associated with a mechanism down-regulating production of 11β-HSD1 activity. |
doi_str_mv | 10.1016/0303-7207(93)90015-C |
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The 11β-HSD1B mRNA was found exclusively in the kidney, predominantly localized within the medulla with low amounts of the message in the cortex. Neither the renal papilla nor a range of peripheral and central tissues showed evidence of 11β-HSD1B mRNA. Expression of the whole (11β-HSD1A) and truncated enzymes in COS cells resulted in immunoreactive 34 kDa and 26 kDa proteins respectively, while kidney homogenates showed 34 kDa and 40 kDa species. The 11β-HSD1A enzyme converted corticosterone and cortisol to their respective 11-dehydro metabolites with an absolute dependence on NADP as co-factor, while the 26 kDa 11β-HSD1B protein was unable to metabolize either steroid. These results suggest that transcription of the 11β-HSD1B mRNA is associated with a mechanism down-regulating production of 11β-HSD1 activity.</description><identifier>ISSN: 0303-7207</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/0303-7207(93)90015-C</identifier><identifier>PMID: 8319828</identifier><identifier>CODEN: MCEND6</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>11-beta-Hydroxysteroid Dehydrogenases ; 11β-Hydroxysteroid dehydrogenase ; Animals ; Biological and medical sciences ; Cell Line ; Cercopithecus aethiops ; Corticosterone - metabolism ; DNA - genetics ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Enzymologic ; Glucocorticoid ; Hydrocortisone - metabolism ; Hydroxysteroid Dehydrogenases - genetics ; Hydroxysteroid Dehydrogenases - metabolism ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Kidney ; Kidney Cortex - enzymology ; Kidney Medulla - enzymology ; Mineralocorticoid receptor ; Molecular Weight ; NADP - metabolism ; Organ Specificity ; Rat ; Rats ; Recombinant Fusion Proteins - biosynthesis ; RNA, Messenger - analysis ; RNA, Messenger - genetics ; Substrate Specificity ; Type I receptor ; Vertebrates: urinary system</subject><ispartof>Molecular and cellular endocrinology, 1993-04, Vol.92 (2), p.247-251</ispartof><rights>1993</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-2a022e1bfe4f5719d63783090e0fda369031e1302a2d22b9185f85513fbf5ebf3</citedby><cites>FETCH-LOGICAL-c417t-2a022e1bfe4f5719d63783090e0fda369031e1302a2d22b9185f85513fbf5ebf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/030372079390015C$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4708420$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8319828$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mercer, Wendy</creatorcontrib><creatorcontrib>Obeyesekere, Varuni</creatorcontrib><creatorcontrib>Smith, Robin</creatorcontrib><creatorcontrib>Krozowski, Zygmunt</creatorcontrib><title>Characterization of 11β-HSD1B gene expression and enzymatic activity</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>Nuclease protection analysis has been used to study the distribution of an mRNA that has been predicted to give rise to a truncated form of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD1B). The 11β-HSD1B mRNA was found exclusively in the kidney, predominantly localized within the medulla with low amounts of the message in the cortex. Neither the renal papilla nor a range of peripheral and central tissues showed evidence of 11β-HSD1B mRNA. Expression of the whole (11β-HSD1A) and truncated enzymes in COS cells resulted in immunoreactive 34 kDa and 26 kDa proteins respectively, while kidney homogenates showed 34 kDa and 40 kDa species. The 11β-HSD1A enzyme converted corticosterone and cortisol to their respective 11-dehydro metabolites with an absolute dependence on NADP as co-factor, while the 26 kDa 11β-HSD1B protein was unable to metabolize either steroid. These results suggest that transcription of the 11β-HSD1B mRNA is associated with a mechanism down-regulating production of 11β-HSD1 activity.</description><subject>11-beta-Hydroxysteroid Dehydrogenases</subject><subject>11β-Hydroxysteroid dehydrogenase</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cercopithecus aethiops</subject><subject>Corticosterone - metabolism</subject><subject>DNA - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Glucocorticoid</subject><subject>Hydrocortisone - metabolism</subject><subject>Hydroxysteroid Dehydrogenases - genetics</subject><subject>Hydroxysteroid Dehydrogenases - metabolism</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Kidney</subject><subject>Kidney Cortex - enzymology</subject><subject>Kidney Medulla - enzymology</subject><subject>Mineralocorticoid receptor</subject><subject>Molecular Weight</subject><subject>NADP - metabolism</subject><subject>Organ Specificity</subject><subject>Rat</subject><subject>Rats</subject><subject>Recombinant Fusion Proteins - biosynthesis</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - genetics</subject><subject>Substrate Specificity</subject><subject>Type I receptor</subject><subject>Vertebrates: urinary system</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1u1DAUhS0EKkPLGxQpC4RgkXKvHcf2phKE_kmVWBTWluNcF6OZZLAzVaeP1QfpM5HpjGYJq7s43zm6-hg7RjhBwPozCBCl4qA-GvHJAKAsmxdshlrxUoNUL9lsj7xmb3L-DQBKcn3ADrRAo7mesbPml0vOj5Tigxvj0BdDKBCfHsvLm2_4tbilngq6XybKeZO6viuof1gvJtgXUzHexXF9xF4FN8_0dncP2c_zsx_NZXn9_eKq-XJd-grVWHIHnBO2gaogFZquFkoLMEAQOidqAwIJBXDHO85bg1oGLSWK0AZJbRCH7MN2d5mGPyvKo13E7Gk-dz0Nq2yV1Cg5mv-CWNdGIfAJrLagT0POiYJdprhwaW0R7Eaz3Ti0G4fWCPus2TZT7d1uf9UuqNuXdl6n_P0ud9m7eUiu9zHvsUqBrjhM2OkWo0naXaRks4_Ue-piIj_aboj__uMvghuXiQ</recordid><startdate>19930401</startdate><enddate>19930401</enddate><creator>Mercer, Wendy</creator><creator>Obeyesekere, Varuni</creator><creator>Smith, Robin</creator><creator>Krozowski, Zygmunt</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>19930401</creationdate><title>Characterization of 11β-HSD1B gene expression and enzymatic activity</title><author>Mercer, Wendy ; Obeyesekere, Varuni ; Smith, Robin ; Krozowski, Zygmunt</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-2a022e1bfe4f5719d63783090e0fda369031e1302a2d22b9185f85513fbf5ebf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>11-beta-Hydroxysteroid Dehydrogenases</topic><topic>11β-Hydroxysteroid dehydrogenase</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cercopithecus aethiops</topic><topic>Corticosterone - metabolism</topic><topic>DNA - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Glucocorticoid</topic><topic>Hydrocortisone - metabolism</topic><topic>Hydroxysteroid Dehydrogenases - genetics</topic><topic>Hydroxysteroid Dehydrogenases - metabolism</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Kidney</topic><topic>Kidney Cortex - enzymology</topic><topic>Kidney Medulla - enzymology</topic><topic>Mineralocorticoid receptor</topic><topic>Molecular Weight</topic><topic>NADP - metabolism</topic><topic>Organ Specificity</topic><topic>Rat</topic><topic>Rats</topic><topic>Recombinant Fusion Proteins - biosynthesis</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - genetics</topic><topic>Substrate Specificity</topic><topic>Type I receptor</topic><topic>Vertebrates: urinary system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mercer, Wendy</creatorcontrib><creatorcontrib>Obeyesekere, Varuni</creatorcontrib><creatorcontrib>Smith, Robin</creatorcontrib><creatorcontrib>Krozowski, Zygmunt</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mercer, Wendy</au><au>Obeyesekere, Varuni</au><au>Smith, Robin</au><au>Krozowski, Zygmunt</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of 11β-HSD1B gene expression and enzymatic activity</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>1993-04-01</date><risdate>1993</risdate><volume>92</volume><issue>2</issue><spage>247</spage><epage>251</epage><pages>247-251</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><coden>MCEND6</coden><abstract>Nuclease protection analysis has been used to study the distribution of an mRNA that has been predicted to give rise to a truncated form of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD1B). The 11β-HSD1B mRNA was found exclusively in the kidney, predominantly localized within the medulla with low amounts of the message in the cortex. Neither the renal papilla nor a range of peripheral and central tissues showed evidence of 11β-HSD1B mRNA. Expression of the whole (11β-HSD1A) and truncated enzymes in COS cells resulted in immunoreactive 34 kDa and 26 kDa proteins respectively, while kidney homogenates showed 34 kDa and 40 kDa species. The 11β-HSD1A enzyme converted corticosterone and cortisol to their respective 11-dehydro metabolites with an absolute dependence on NADP as co-factor, while the 26 kDa 11β-HSD1B protein was unable to metabolize either steroid. These results suggest that transcription of the 11β-HSD1B mRNA is associated with a mechanism down-regulating production of 11β-HSD1 activity.</abstract><cop>Shannon</cop><pub>Elsevier Ireland Ltd</pub><pmid>8319828</pmid><doi>10.1016/0303-7207(93)90015-C</doi><tpages>5</tpages></addata></record> |
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subjects | 11-beta-Hydroxysteroid Dehydrogenases 11β-Hydroxysteroid dehydrogenase Animals Biological and medical sciences Cell Line Cercopithecus aethiops Corticosterone - metabolism DNA - genetics Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Enzymologic Glucocorticoid Hydrocortisone - metabolism Hydroxysteroid Dehydrogenases - genetics Hydroxysteroid Dehydrogenases - metabolism Isoenzymes - genetics Isoenzymes - metabolism Kidney Kidney Cortex - enzymology Kidney Medulla - enzymology Mineralocorticoid receptor Molecular Weight NADP - metabolism Organ Specificity Rat Rats Recombinant Fusion Proteins - biosynthesis RNA, Messenger - analysis RNA, Messenger - genetics Substrate Specificity Type I receptor Vertebrates: urinary system |
title | Characterization of 11β-HSD1B gene expression and enzymatic activity |
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