Prostate Hyperplasia in a Transgenic Mouse with Prostate-Specific Expression of Prolactin
Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expressio...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2003-06, Vol.144 (6), p.2269-2278 |
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| creator | Kindblom, Jon Dillner, Karin Sahlin, Lena Robertson, Fiona Ormandy, Christopher Törnell, Jan Wennbo, Håkan |
| description | Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels. |
| doi_str_mv | 10.1210/en.2002-0187 |
| format | Article |
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We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2002-0187</identifier><identifier>PMID: 12746285</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Age ; analysis ; Androgen ; Androgens ; Animals ; Biological and medical sciences ; blood ; Cell and Molecular Biology ; Cell Count ; Cell- och molekylärbiologi ; chemistry ; Enlargement ; Epithelial Cells ; Epithelial Cells - pathology ; Estrogen ; Fundamental and applied biological sciences. Psychology ; Fysiologi ; Gene Expression ; Gene Expression - physiology ; genetics ; Hyperplasia ; Hyperprolactinemia ; Immunohistochemistry ; Inbred C57BL ; Inbred CBA ; Lobes ; Male ; Medicin och hälsovetenskap ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Transgenic ; Morphogenesis ; pathology ; Physiology ; physiopathology ; Polypeptides ; Prolactin ; Prolactin - blood ; Prolactin - genetics ; Prostate ; Prostate - chemistry ; Prostate - pathology ; Prostate - physiology ; Prostatic Hyperplasia ; Prostatic Hyperplasia - pathology ; Prostatic Hyperplasia - physiopathology ; Receptors ; Receptors, Androgen - analysis ; Receptors, Estrogen - analysis ; Stroma ; Stromal Cells ; Stromal Cells - chemistry ; Stromal Cells - pathology ; Testosterone ; Testosterone - blood ; Transgenes ; Transgenes - genetics ; Transgenic ; Transgenic animals ; Transgenic mice</subject><ispartof>Endocrinology (Philadelphia), 2003-06, Vol.144 (6), p.2269-2278</ispartof><rights>Copyright © 2003 by The Endocrine Society 2003</rights><rights>2003 INIST-CNRS</rights><rights>Copyright © 2003 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c583t-4893c628617c025501b6000abe69c6295beac85f80345fb2f8e59dce45be348f3</citedby><cites>FETCH-LOGICAL-c583t-4893c628617c025501b6000abe69c6295beac85f80345fb2f8e59dce45be348f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14829774$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12746285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/164466$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1932816$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Kindblom, Jon</creatorcontrib><creatorcontrib>Dillner, Karin</creatorcontrib><creatorcontrib>Sahlin, Lena</creatorcontrib><creatorcontrib>Robertson, Fiona</creatorcontrib><creatorcontrib>Ormandy, Christopher</creatorcontrib><creatorcontrib>Törnell, Jan</creatorcontrib><creatorcontrib>Wennbo, Håkan</creatorcontrib><title>Prostate Hyperplasia in a Transgenic Mouse with Prostate-Specific Expression of Prolactin</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.</description><subject>Age</subject><subject>analysis</subject><subject>Androgen</subject><subject>Androgens</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>blood</subject><subject>Cell and Molecular Biology</subject><subject>Cell Count</subject><subject>Cell- och molekylärbiologi</subject><subject>chemistry</subject><subject>Enlargement</subject><subject>Epithelial Cells</subject><subject>Epithelial Cells - pathology</subject><subject>Estrogen</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fysiologi</subject><subject>Gene Expression</subject><subject>Gene Expression - physiology</subject><subject>genetics</subject><subject>Hyperplasia</subject><subject>Hyperprolactinemia</subject><subject>Immunohistochemistry</subject><subject>Inbred C57BL</subject><subject>Inbred CBA</subject><subject>Lobes</subject><subject>Male</subject><subject>Medicin och hälsovetenskap</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred CBA</subject><subject>Mice, Transgenic</subject><subject>Morphogenesis</subject><subject>pathology</subject><subject>Physiology</subject><subject>physiopathology</subject><subject>Polypeptides</subject><subject>Prolactin</subject><subject>Prolactin - blood</subject><subject>Prolactin - genetics</subject><subject>Prostate</subject><subject>Prostate - chemistry</subject><subject>Prostate - pathology</subject><subject>Prostate - physiology</subject><subject>Prostatic Hyperplasia</subject><subject>Prostatic Hyperplasia - pathology</subject><subject>Prostatic Hyperplasia - physiopathology</subject><subject>Receptors</subject><subject>Receptors, Androgen - analysis</subject><subject>Receptors, Estrogen - analysis</subject><subject>Stroma</subject><subject>Stromal Cells</subject><subject>Stromal Cells - chemistry</subject><subject>Stromal Cells - pathology</subject><subject>Testosterone</subject><subject>Testosterone - blood</subject><subject>Transgenes</subject><subject>Transgenes - genetics</subject><subject>Transgenic</subject><subject>Transgenic animals</subject><subject>Transgenic mice</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kk1v1DAQhi0EokvhxhlFQqUXUvwZ20dUlRapFUiUAyfL8U4Wl6wT7ERt_z1Ok7ISajnZnnlm5h3PIPSa4CNCCf4A4YhiTEtMlHyCVkRzUUoi8VO0wpiwUlIq99CLlK7yk3POnqM9QiWvqBIr9ONr7NJgByjObnuIfWuTt4UPhS0uow1pA8G74qIbExTXfvhZ3PPltx6cb7Lz5KaPkJLvQtE1k7-1bvDhJXrW2DbBq-XcR98_nVwen5XnX04_H388L51QbCi50sxlLRWRDlMhMKkrjLGtodLZrkUN1inRKMy4aGraKBB67YBnB-OqYfuonPOma-jH2vTRb228NZ31ZjH9yjcwQmmldeblo3wfu_Uu6D6QaEYVqf5baTP2Jps2411AxXk18e9mPqf9PUIazNYnB21rA-QPNZIxTPJIMvj2H_CqG2PIv2YYYVgIjqXM1PuZcnkEKULzVwDBZloFA8FMq2CmVcj4myXpWG9hvYOX2WfgYAFscrZt8ridTzuOK6qlnNQdzlyXe3ykZLmUZDMJYd256APcbcaumweF_gF3adn_</recordid><startdate>20030601</startdate><enddate>20030601</enddate><creator>Kindblom, Jon</creator><creator>Dillner, Karin</creator><creator>Sahlin, Lena</creator><creator>Robertson, Fiona</creator><creator>Ormandy, Christopher</creator><creator>Törnell, Jan</creator><creator>Wennbo, Håkan</creator><general>Endocrine Society</general><general>Oxford University Press</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>F1U</scope></search><sort><creationdate>20030601</creationdate><title>Prostate Hyperplasia in a Transgenic Mouse with Prostate-Specific Expression of Prolactin</title><author>Kindblom, Jon ; Dillner, Karin ; Sahlin, Lena ; Robertson, Fiona ; Ormandy, Christopher ; Törnell, Jan ; Wennbo, Håkan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c583t-4893c628617c025501b6000abe69c6295beac85f80345fb2f8e59dce45be348f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Age</topic><topic>analysis</topic><topic>Androgen</topic><topic>Androgens</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>blood</topic><topic>Cell and Molecular Biology</topic><topic>Cell Count</topic><topic>Cell- och molekylärbiologi</topic><topic>chemistry</topic><topic>Enlargement</topic><topic>Epithelial Cells</topic><topic>Epithelial Cells - pathology</topic><topic>Estrogen</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fysiologi</topic><topic>Gene Expression</topic><topic>Gene Expression - physiology</topic><topic>genetics</topic><topic>Hyperplasia</topic><topic>Hyperprolactinemia</topic><topic>Immunohistochemistry</topic><topic>Inbred C57BL</topic><topic>Inbred CBA</topic><topic>Lobes</topic><topic>Male</topic><topic>Medicin och hälsovetenskap</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred CBA</topic><topic>Mice, Transgenic</topic><topic>Morphogenesis</topic><topic>pathology</topic><topic>Physiology</topic><topic>physiopathology</topic><topic>Polypeptides</topic><topic>Prolactin</topic><topic>Prolactin - blood</topic><topic>Prolactin - genetics</topic><topic>Prostate</topic><topic>Prostate - chemistry</topic><topic>Prostate - pathology</topic><topic>Prostate - physiology</topic><topic>Prostatic Hyperplasia</topic><topic>Prostatic Hyperplasia - pathology</topic><topic>Prostatic Hyperplasia - physiopathology</topic><topic>Receptors</topic><topic>Receptors, Androgen - analysis</topic><topic>Receptors, Estrogen - analysis</topic><topic>Stroma</topic><topic>Stromal Cells</topic><topic>Stromal Cells - chemistry</topic><topic>Stromal Cells - pathology</topic><topic>Testosterone</topic><topic>Testosterone - blood</topic><topic>Transgenes</topic><topic>Transgenes - genetics</topic><topic>Transgenic</topic><topic>Transgenic animals</topic><topic>Transgenic mice</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kindblom, Jon</creatorcontrib><creatorcontrib>Dillner, Karin</creatorcontrib><creatorcontrib>Sahlin, Lena</creatorcontrib><creatorcontrib>Robertson, Fiona</creatorcontrib><creatorcontrib>Ormandy, Christopher</creatorcontrib><creatorcontrib>Törnell, Jan</creatorcontrib><creatorcontrib>Wennbo, Håkan</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>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Göteborgs universitet</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kindblom, Jon</au><au>Dillner, Karin</au><au>Sahlin, Lena</au><au>Robertson, Fiona</au><au>Ormandy, Christopher</au><au>Törnell, Jan</au><au>Wennbo, Håkan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prostate Hyperplasia in a Transgenic Mouse with Prostate-Specific Expression of Prolactin</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2003-06-01</date><risdate>2003</risdate><volume>144</volume><issue>6</issue><spage>2269</spage><epage>2278</epage><pages>2269-2278</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>12746285</pmid><doi>10.1210/en.2002-0187</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Endocrinology (Philadelphia), 2003-06, Vol.144 (6), p.2269-2278 |
| issn | 0013-7227 1945-7170 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Age analysis Androgen Androgens Animals Biological and medical sciences blood Cell and Molecular Biology Cell Count Cell- och molekylärbiologi chemistry Enlargement Epithelial Cells Epithelial Cells - pathology Estrogen Fundamental and applied biological sciences. Psychology Fysiologi Gene Expression Gene Expression - physiology genetics Hyperplasia Hyperprolactinemia Immunohistochemistry Inbred C57BL Inbred CBA Lobes Male Medicin och hälsovetenskap Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Transgenic Morphogenesis pathology Physiology physiopathology Polypeptides Prolactin Prolactin - blood Prolactin - genetics Prostate Prostate - chemistry Prostate - pathology Prostate - physiology Prostatic Hyperplasia Prostatic Hyperplasia - pathology Prostatic Hyperplasia - physiopathology Receptors Receptors, Androgen - analysis Receptors, Estrogen - analysis Stroma Stromal Cells Stromal Cells - chemistry Stromal Cells - pathology Testosterone Testosterone - blood Transgenes Transgenes - genetics Transgenic Transgenic animals Transgenic mice |
| title | Prostate Hyperplasia in a Transgenic Mouse with Prostate-Specific Expression of Prolactin |
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