11 beta-hydroxysteroid dehydrogenase type 1 is a predominant 11 beta-reductase in the intact perfused rat liver
11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1), a regulator of intrahepatocellular glucocorticoid activity, is bidirectional in homogenates but catalyses 11 beta-reduction (regenerating glucocorticoid) in intact primary hepatocytes in culture. To examine this discrepancy at the whole-or...
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| Veröffentlicht in: | Journal of endocrinology 2000-06, Vol.165 (3), p.685-692 |
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| container_title | Journal of endocrinology |
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| creator | Jamieson, PM Walker, BR Chapman, KE Andrew, R Rossiter, S Seckl |
| description | 11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1), a regulator of intrahepatocellular glucocorticoid activity, is bidirectional in homogenates but catalyses 11 beta-reduction (regenerating glucocorticoid) in intact primary hepatocytes in culture. To examine this discrepancy at the whole-organ level, we examined 11 beta-HSD-1 activity in the intact bivascularly perfused rat liver. On a single pass through male rat liver, 44+/-5% of 11-dehydrocorticosterone (11-DHC) recovered was 11 beta-reduced to corticosterone, whereas 10+/-1% of corticosterone was 11 beta-dehydrogenated to 11-DHC. 11 beta-Reduction was less in female liver (21+/-2%, P |
| doi_str_mv | 10.1677/joe.0.1650685 |
| format | Article |
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To examine this discrepancy at the whole-organ level, we examined 11 beta-HSD-1 activity in the intact bivascularly perfused rat liver. On a single pass through male rat liver, 44+/-5% of 11-dehydrocorticosterone (11-DHC) recovered was 11 beta-reduced to corticosterone, whereas 10+/-1% of corticosterone was 11 beta-dehydrogenated to 11-DHC. 11 beta-Reduction was less in female liver (21+/-2%, P<0.01) and was significantly greater with perfusion of all substrate via the portal vein (50+/-3%) than via the hepatic artery (30+/-2%, P<0.05). 11 beta-Reductase activity was not saturated by 11-DHC (10(-)(9)-10(-)(6) M). Perfusion with carbenoxolone (CBX, 10(-)(6)-10(-)(3 )M) did not alter 11 beta-reduction of 11-DHC. In contrast, pretreatment with CBX in vivo (10 mg/day) for 7 days inhibited 11 beta-reductase (19+/-4% conversion, P<0.01). Concentrations of 11-DHC in male rat plasma were 44+/-6 nM. Thus 11 beta-HSD-1 is predominantly an 11 beta-reductase in the intact rat liver and is only inhibited by chronic administration of CBX. The substantial concentrations of plasma 11-DHC as substrate suggest that 11 beta-HSD-1 activity and its potential selective inhibition could modify glucocorticoid action in vivo.</description><identifier>ISSN: 0022-0795</identifier><identifier>EISSN: 1479-6805</identifier><identifier>DOI: 10.1677/joe.0.1650685</identifier><identifier>PMID: 10828853</identifier><language>eng</language><publisher>England: BioScientifica</publisher><subject>11-beta-Hydroxysteroid Dehydrogenases ; Animals ; Carbenoxolone - pharmacology ; Corticosterone - analogs & derivatives ; Corticosterone - blood ; Dose-Response Relationship, Drug ; Female ; Hydroxysteroid Dehydrogenases - antagonists & inhibitors ; Hydroxysteroid Dehydrogenases - metabolism ; Liver - enzymology ; Male ; Rats ; Sex Characteristics</subject><ispartof>Journal of endocrinology, 2000-06, Vol.165 (3), p.685-692</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b415t-c02f0f557ad5a8050f56d16d572b44eda6291316ec82969b75d29545be9dffb3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10828853$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jamieson, PM</creatorcontrib><creatorcontrib>Walker, BR</creatorcontrib><creatorcontrib>Chapman, KE</creatorcontrib><creatorcontrib>Andrew, R</creatorcontrib><creatorcontrib>Rossiter, S</creatorcontrib><creatorcontrib>Seckl</creatorcontrib><creatorcontrib>Seckl</creatorcontrib><title>11 beta-hydroxysteroid dehydrogenase type 1 is a predominant 11 beta-reductase in the intact perfused rat liver</title><title>Journal of endocrinology</title><addtitle>J Endocrinol</addtitle><description>11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1), a regulator of intrahepatocellular glucocorticoid activity, is bidirectional in homogenates but catalyses 11 beta-reduction (regenerating glucocorticoid) in intact primary hepatocytes in culture. To examine this discrepancy at the whole-organ level, we examined 11 beta-HSD-1 activity in the intact bivascularly perfused rat liver. On a single pass through male rat liver, 44+/-5% of 11-dehydrocorticosterone (11-DHC) recovered was 11 beta-reduced to corticosterone, whereas 10+/-1% of corticosterone was 11 beta-dehydrogenated to 11-DHC. 11 beta-Reduction was less in female liver (21+/-2%, P<0.01) and was significantly greater with perfusion of all substrate via the portal vein (50+/-3%) than via the hepatic artery (30+/-2%, P<0.05). 11 beta-Reductase activity was not saturated by 11-DHC (10(-)(9)-10(-)(6) M). Perfusion with carbenoxolone (CBX, 10(-)(6)-10(-)(3 )M) did not alter 11 beta-reduction of 11-DHC. In contrast, pretreatment with CBX in vivo (10 mg/day) for 7 days inhibited 11 beta-reductase (19+/-4% conversion, P<0.01). Concentrations of 11-DHC in male rat plasma were 44+/-6 nM. Thus 11 beta-HSD-1 is predominantly an 11 beta-reductase in the intact rat liver and is only inhibited by chronic administration of CBX. The substantial concentrations of plasma 11-DHC as substrate suggest that 11 beta-HSD-1 activity and its potential selective inhibition could modify glucocorticoid action in vivo.</description><subject>11-beta-Hydroxysteroid Dehydrogenases</subject><subject>Animals</subject><subject>Carbenoxolone - pharmacology</subject><subject>Corticosterone - analogs & derivatives</subject><subject>Corticosterone - blood</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Hydroxysteroid Dehydrogenases - antagonists & inhibitors</subject><subject>Hydroxysteroid Dehydrogenases - metabolism</subject><subject>Liver - enzymology</subject><subject>Male</subject><subject>Rats</subject><subject>Sex Characteristics</subject><issn>0022-0795</issn><issn>1479-6805</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM9LwzAYhoMobk6PXiUnb51J2yTtUYa_YOBl95I2X9eMrqlJqva_t10niKCn7-Xj-V6SB6FrSpaUC3G3M7AcIyM8YSdoTmORBjwh7BTNCQnDgIiUzdCFcztCKKMiOkczSpIwSVg0R4ZSnIOXQdUraz5758EarbCCw2ILjXSAfd8Cplg7LHFrQZm9bmTj8ffxsOoKP5K6wb4ah5eFxy3YsnOgsJUe1_od7CU6K2Xt4Oo4F2jz-LBZPQfr16eX1f06yGPKfFCQsCQlY0IqJofPDJkryhUTYR7HoCQPUxpRDkUSpjzNBVNhymKWQ6rKMo8W6Haqba1568D5bK9dAXUtGzCdywSlyeCAD2AwgYU1zlkos9bqvbR9Rkk2Cs4GwdkYD4IH_uZY3OV7UD_oyegAxBNQ6W31oS1kuTau0NB4XepC_tkbTWe_6P9f8wVbhJnS</recordid><startdate>20000601</startdate><enddate>20000601</enddate><creator>Jamieson, PM</creator><creator>Walker, BR</creator><creator>Chapman, KE</creator><creator>Andrew, R</creator><creator>Rossiter, S</creator><creator>Seckl</creator><general>BioScientifica</general><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>7X8</scope></search><sort><creationdate>20000601</creationdate><title>11 beta-hydroxysteroid dehydrogenase type 1 is a predominant 11 beta-reductase in the intact perfused rat liver</title><author>Jamieson, PM ; Walker, BR ; Chapman, KE ; Andrew, R ; Rossiter, S ; Seckl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b415t-c02f0f557ad5a8050f56d16d572b44eda6291316ec82969b75d29545be9dffb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>11-beta-Hydroxysteroid Dehydrogenases</topic><topic>Animals</topic><topic>Carbenoxolone - pharmacology</topic><topic>Corticosterone - analogs & derivatives</topic><topic>Corticosterone - blood</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Hydroxysteroid Dehydrogenases - antagonists & inhibitors</topic><topic>Hydroxysteroid Dehydrogenases - metabolism</topic><topic>Liver - enzymology</topic><topic>Male</topic><topic>Rats</topic><topic>Sex Characteristics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jamieson, PM</creatorcontrib><creatorcontrib>Walker, BR</creatorcontrib><creatorcontrib>Chapman, KE</creatorcontrib><creatorcontrib>Andrew, R</creatorcontrib><creatorcontrib>Rossiter, S</creatorcontrib><creatorcontrib>Seckl</creatorcontrib><creatorcontrib>Seckl</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jamieson, PM</au><au>Walker, BR</au><au>Chapman, KE</au><au>Andrew, R</au><au>Rossiter, S</au><au>Seckl</au><aucorp>Seckl</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>11 beta-hydroxysteroid dehydrogenase type 1 is a predominant 11 beta-reductase in the intact perfused rat liver</atitle><jtitle>Journal of endocrinology</jtitle><addtitle>J Endocrinol</addtitle><date>2000-06-01</date><risdate>2000</risdate><volume>165</volume><issue>3</issue><spage>685</spage><epage>692</epage><pages>685-692</pages><issn>0022-0795</issn><eissn>1479-6805</eissn><abstract>11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1), a regulator of intrahepatocellular glucocorticoid activity, is bidirectional in homogenates but catalyses 11 beta-reduction (regenerating glucocorticoid) in intact primary hepatocytes in culture. To examine this discrepancy at the whole-organ level, we examined 11 beta-HSD-1 activity in the intact bivascularly perfused rat liver. On a single pass through male rat liver, 44+/-5% of 11-dehydrocorticosterone (11-DHC) recovered was 11 beta-reduced to corticosterone, whereas 10+/-1% of corticosterone was 11 beta-dehydrogenated to 11-DHC. 11 beta-Reduction was less in female liver (21+/-2%, P<0.01) and was significantly greater with perfusion of all substrate via the portal vein (50+/-3%) than via the hepatic artery (30+/-2%, P<0.05). 11 beta-Reductase activity was not saturated by 11-DHC (10(-)(9)-10(-)(6) M). Perfusion with carbenoxolone (CBX, 10(-)(6)-10(-)(3 )M) did not alter 11 beta-reduction of 11-DHC. In contrast, pretreatment with CBX in vivo (10 mg/day) for 7 days inhibited 11 beta-reductase (19+/-4% conversion, P<0.01). Concentrations of 11-DHC in male rat plasma were 44+/-6 nM. Thus 11 beta-HSD-1 is predominantly an 11 beta-reductase in the intact rat liver and is only inhibited by chronic administration of CBX. The substantial concentrations of plasma 11-DHC as substrate suggest that 11 beta-HSD-1 activity and its potential selective inhibition could modify glucocorticoid action in vivo.</abstract><cop>England</cop><pub>BioScientifica</pub><pmid>10828853</pmid><doi>10.1677/joe.0.1650685</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 11-beta-Hydroxysteroid Dehydrogenases Animals Carbenoxolone - pharmacology Corticosterone - analogs & derivatives Corticosterone - blood Dose-Response Relationship, Drug Female Hydroxysteroid Dehydrogenases - antagonists & inhibitors Hydroxysteroid Dehydrogenases - metabolism Liver - enzymology Male Rats Sex Characteristics |
| title | 11 beta-hydroxysteroid dehydrogenase type 1 is a predominant 11 beta-reductase in the intact perfused rat liver |
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