In vivo mouse model for analysis of hydroxysteroid (17β) dehydrogenase 1 inhibitors
Hydroxysteroid (17β) dehydrogenase 1 (HSD17B1) catalyzes the reaction between the low active 17-ketosteroids and the highly active 17beta-hydroxysteroids. In the present study, we have generated transgenic (TG) mice expressing human (h) HSD17B1 under mouse mammary tumor virus (MMTV) promoter (MMTV-h...
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| Veröffentlicht in: | Molecular and cellular endocrinology 2009-03, Vol.301 (1), p.158-162 |
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| container_title | Molecular and cellular endocrinology |
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| creator | Lamminen, Tarja Saloniemi, Taija Huhtinen, Kaisa Koskimies, Pasi Messinger, Josef Husen, Bettina Thole, Hubert Poutanen, Matti |
| description | Hydroxysteroid (17β) dehydrogenase 1 (HSD17B1) catalyzes the reaction between the low active 17-ketosteroids and the highly active 17beta-hydroxysteroids. In the present study, we have generated transgenic (TG) mice expressing human (h) HSD17B1 under mouse mammary tumor virus (MMTV) promoter (MMTV-hHSD17B1TG mice). The MMTV-hHSD17B1TG mice were used to characterize HSD17B1 enzyme activity and properties of HSD17B1 inhibitor
in vivo. Expression of the transgene was detected by enzyme activity and RT-PCR analysis. Increased HSD17B1 activity in the TG mice was detected
in vivo by applying estrone as a substrate via an intravenous injection. The developed enzyme activity measurement was then applied to analyze the efficacy of HSD17B1 inhibitor
in vivo. The results indicated that the MMTV-hHSD17B1TG mouse model is a valuable novel tool to test human HSD17B1 inhibition by various compounds
in vivo. With the potent hHSD17B1 inhibitor compound tested, at highest an 85% and 33% inhibition of the enzyme activity in males and in females, respectively, was observed. |
| doi_str_mv | 10.1016/j.mce.2008.10.034 |
| format | Article |
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in vivo. Expression of the transgene was detected by enzyme activity and RT-PCR analysis. Increased HSD17B1 activity in the TG mice was detected
in vivo by applying estrone as a substrate via an intravenous injection. The developed enzyme activity measurement was then applied to analyze the efficacy of HSD17B1 inhibitor
in vivo. The results indicated that the MMTV-hHSD17B1TG mouse model is a valuable novel tool to test human HSD17B1 inhibition by various compounds
in vivo. With the potent hHSD17B1 inhibitor compound tested, at highest an 85% and 33% inhibition of the enzyme activity in males and in females, respectively, was observed.</description><identifier>ISSN: 0303-7207</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/j.mce.2008.10.034</identifier><identifier>PMID: 19026716</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>17-Hydroxysteroid Dehydrogenases - antagonists & inhibitors ; Animals ; Biocompatibility ; Biomedical materials ; Enzyme activity ; Enzyme Inhibitors - analysis ; Enzyme Inhibitors - pharmacology ; Female ; Gene Expression Profiling ; Humans ; Hydroxysteroid (17β) dehydrogenase ; In vivo testing ; In vivo tests ; Inhibitor ; Inhibitors ; Male ; Mammary Tumor Virus, Mouse - genetics ; Mice ; Mice, Transgenic ; Models, Animal ; Promoter Regions, Genetic - genetics ; Surgical implants ; Transgenes ; Transgenic mouse</subject><ispartof>Molecular and cellular endocrinology, 2009-03, Vol.301 (1), p.158-162</ispartof><rights>2008 Elsevier Ireland Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c383t-adb4b7510612afc6fc7c58ff9073a1fe6033d5c188933cfcbf07beb201c0c56c3</citedby><cites>FETCH-LOGICAL-c383t-adb4b7510612afc6fc7c58ff9073a1fe6033d5c188933cfcbf07beb201c0c56c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mce.2008.10.034$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19026716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lamminen, Tarja</creatorcontrib><creatorcontrib>Saloniemi, Taija</creatorcontrib><creatorcontrib>Huhtinen, Kaisa</creatorcontrib><creatorcontrib>Koskimies, Pasi</creatorcontrib><creatorcontrib>Messinger, Josef</creatorcontrib><creatorcontrib>Husen, Bettina</creatorcontrib><creatorcontrib>Thole, Hubert</creatorcontrib><creatorcontrib>Poutanen, Matti</creatorcontrib><title>In vivo mouse model for analysis of hydroxysteroid (17β) dehydrogenase 1 inhibitors</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>Hydroxysteroid (17β) dehydrogenase 1 (HSD17B1) catalyzes the reaction between the low active 17-ketosteroids and the highly active 17beta-hydroxysteroids. In the present study, we have generated transgenic (TG) mice expressing human (h) HSD17B1 under mouse mammary tumor virus (MMTV) promoter (MMTV-hHSD17B1TG mice). The MMTV-hHSD17B1TG mice were used to characterize HSD17B1 enzyme activity and properties of HSD17B1 inhibitor
in vivo. Expression of the transgene was detected by enzyme activity and RT-PCR analysis. Increased HSD17B1 activity in the TG mice was detected
in vivo by applying estrone as a substrate via an intravenous injection. The developed enzyme activity measurement was then applied to analyze the efficacy of HSD17B1 inhibitor
in vivo. The results indicated that the MMTV-hHSD17B1TG mouse model is a valuable novel tool to test human HSD17B1 inhibition by various compounds
in vivo. With the potent hHSD17B1 inhibitor compound tested, at highest an 85% and 33% inhibition of the enzyme activity in males and in females, respectively, was observed.</description><subject>17-Hydroxysteroid Dehydrogenases - antagonists & inhibitors</subject><subject>Animals</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Enzyme activity</subject><subject>Enzyme Inhibitors - analysis</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Hydroxysteroid (17β) dehydrogenase</subject><subject>In vivo testing</subject><subject>In vivo tests</subject><subject>Inhibitor</subject><subject>Inhibitors</subject><subject>Male</subject><subject>Mammary Tumor Virus, Mouse - genetics</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Models, Animal</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Surgical implants</subject><subject>Transgenes</subject><subject>Transgenic mouse</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFOGzEQhq2qqATaB-il8qmFw6bjddb2ihOKgCIhcYGz5bXHxdHumtqbiLwWD9Jnwmki9cZlrBl9_y_5I-QrgzkDJn6u5oPFeQ2gyj4HvvhAZkzJulLQyI9kBhx4JWuQx-Qk5xUAyKZWn8gxa6EWkokZebgd6SZsIh3iOmOZDnvqY6JmNP02h0yjp09bl-LLNk-YYnD0jMm_r-fU4b_7bxxNSTIaxqfQhSmm_JkcedNn_HJ4T8nj9dXD8ld1d39zu7y8qyxXfKqM6xadbBgIVhtvhbfSNsr7FiQ3zKMAzl1jmVIt59bbzoPssKuBWbCNsPyU_Nj3Pqf4Z4150kPIFvvejFi-o1UrmAJeq0J-f5cUom34opUFZHvQpphzQq-fUxhM2moGeiddr3SRrnfSd6civWS-HcrX3YDuf-JguQAXewCLjE3ApLMNOFp0IaGdtIvhnfo3QIiS3A</recordid><startdate>20090325</startdate><enddate>20090325</enddate><creator>Lamminen, Tarja</creator><creator>Saloniemi, Taija</creator><creator>Huhtinen, Kaisa</creator><creator>Koskimies, Pasi</creator><creator>Messinger, Josef</creator><creator>Husen, Bettina</creator><creator>Thole, Hubert</creator><creator>Poutanen, Matti</creator><general>Elsevier Ireland Ltd</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><scope>7U5</scope><scope>8FD</scope><scope>L7M</scope></search><sort><creationdate>20090325</creationdate><title>In vivo mouse model for analysis of hydroxysteroid (17β) dehydrogenase 1 inhibitors</title><author>Lamminen, Tarja ; Saloniemi, Taija ; Huhtinen, Kaisa ; Koskimies, Pasi ; Messinger, Josef ; Husen, Bettina ; Thole, Hubert ; Poutanen, Matti</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c383t-adb4b7510612afc6fc7c58ff9073a1fe6033d5c188933cfcbf07beb201c0c56c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>17-Hydroxysteroid Dehydrogenases - antagonists & inhibitors</topic><topic>Animals</topic><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>Enzyme activity</topic><topic>Enzyme Inhibitors - analysis</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Hydroxysteroid (17β) dehydrogenase</topic><topic>In vivo testing</topic><topic>In vivo tests</topic><topic>Inhibitor</topic><topic>Inhibitors</topic><topic>Male</topic><topic>Mammary Tumor Virus, Mouse - genetics</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Models, Animal</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Surgical implants</topic><topic>Transgenes</topic><topic>Transgenic mouse</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lamminen, Tarja</creatorcontrib><creatorcontrib>Saloniemi, Taija</creatorcontrib><creatorcontrib>Huhtinen, Kaisa</creatorcontrib><creatorcontrib>Koskimies, Pasi</creatorcontrib><creatorcontrib>Messinger, Josef</creatorcontrib><creatorcontrib>Husen, Bettina</creatorcontrib><creatorcontrib>Thole, Hubert</creatorcontrib><creatorcontrib>Poutanen, Matti</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><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Molecular and cellular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lamminen, Tarja</au><au>Saloniemi, Taija</au><au>Huhtinen, Kaisa</au><au>Koskimies, Pasi</au><au>Messinger, Josef</au><au>Husen, Bettina</au><au>Thole, Hubert</au><au>Poutanen, Matti</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo mouse model for analysis of hydroxysteroid (17β) dehydrogenase 1 inhibitors</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>2009-03-25</date><risdate>2009</risdate><volume>301</volume><issue>1</issue><spage>158</spage><epage>162</epage><pages>158-162</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><abstract>Hydroxysteroid (17β) dehydrogenase 1 (HSD17B1) catalyzes the reaction between the low active 17-ketosteroids and the highly active 17beta-hydroxysteroids. In the present study, we have generated transgenic (TG) mice expressing human (h) HSD17B1 under mouse mammary tumor virus (MMTV) promoter (MMTV-hHSD17B1TG mice). The MMTV-hHSD17B1TG mice were used to characterize HSD17B1 enzyme activity and properties of HSD17B1 inhibitor
in vivo. Expression of the transgene was detected by enzyme activity and RT-PCR analysis. Increased HSD17B1 activity in the TG mice was detected
in vivo by applying estrone as a substrate via an intravenous injection. The developed enzyme activity measurement was then applied to analyze the efficacy of HSD17B1 inhibitor
in vivo. The results indicated that the MMTV-hHSD17B1TG mouse model is a valuable novel tool to test human HSD17B1 inhibition by various compounds
in vivo. With the potent hHSD17B1 inhibitor compound tested, at highest an 85% and 33% inhibition of the enzyme activity in males and in females, respectively, was observed.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>19026716</pmid><doi>10.1016/j.mce.2008.10.034</doi><tpages>5</tpages></addata></record> |
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| subjects | 17-Hydroxysteroid Dehydrogenases - antagonists & inhibitors Animals Biocompatibility Biomedical materials Enzyme activity Enzyme Inhibitors - analysis Enzyme Inhibitors - pharmacology Female Gene Expression Profiling Humans Hydroxysteroid (17β) dehydrogenase In vivo testing In vivo tests Inhibitor Inhibitors Male Mammary Tumor Virus, Mouse - genetics Mice Mice, Transgenic Models, Animal Promoter Regions, Genetic - genetics Surgical implants Transgenes Transgenic mouse |
| title | In vivo mouse model for analysis of hydroxysteroid (17β) dehydrogenase 1 inhibitors |
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