Testosterone-stimulated growth of the rat prostate may be driven by tissue hypoxia and hypoxia-inducible factor-1α

Testosterone-stimulated growth of the ventral prostate (VP) in castrated rats is preceded by angiogenesis, but the mechanisms coordinating vascular and tissue growth are unknown. Adult rats were castrated and some treated with testosterone. Tissue hypoxia was studied morphologically using the hypoxi...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of endocrinology 2008-01, Vol.196 (1), p.11-19
Hauptverfasser: Rudolfsson, Stina Häggström, Bergh, Anders
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 19
container_issue 1
container_start_page 11
container_title Journal of endocrinology
container_volume 196
creator Rudolfsson, Stina Häggström
Bergh, Anders
description Testosterone-stimulated growth of the ventral prostate (VP) in castrated rats is preceded by angiogenesis, but the mechanisms coordinating vascular and tissue growth are unknown. Adult rats were castrated and some treated with testosterone. Tissue hypoxia was studied morphologically using the hypoxia marker pimonidazole (Hypoxyprobe), hypoxia-inducible factor-1 (HIF-1) α, vascular endothelial growth factor (VEGF), and carbonicanhydrase 9 (CA-9) levels by western blotting and quantitative RT-PCR. In the intact untreated prostate, most glands were unstained by the hypoxia marker but already 1 day after castration most epithelial cells in the VP were stained. Seven days after castration prostate glands were apparently normoxic again, and HIF-1α, VEGF, and CA-9 were decreased. Treatment of 7-day castrated rats with testosterone resulted in increased epithelial hypoxyprobe staining and increased HIF-1α, VEGF, and CA-9 levels. The transient increase in tissue hypoxia after testosterone treatment is probably caused by a temporary mismatch between oxygen consumption and supply. Treatment of prostate epithelial cells in vitro under normoxic conditions also increased HIF-1α, and this could be blocked if epidermal growth factor receptor (EGFR) signaling was blocked with gefitinib. In vivo gefitinib could, however, not block the testosterone induced increase in HIF-1α. Testosterone may thus induce HIF-1α and its downstream angiogenesis promoting genes by at least two mechanisms, hypoxia and EGFR signaling. Transient epithelial cell hypoxia could by rapidly increasing HIF-1α and VEGF be an essential coordinator of testosterone-stimulated vascular and glandular growth.
doi_str_mv 10.1677/JOE-07-0272
format Article
fullrecord <record><control><sourceid>pascalfrancis_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1677_JOE_07_0272</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20043424</sourcerecordid><originalsourceid>FETCH-LOGICAL-b385t-c195e32791c9fd2991625049d98307fa11604f47afe5a288614329b838b0a8193</originalsourceid><addsrcrecordid>eNp9kU1KBDEQhYMoOv6svEA2riRalXR3kqWIvwhudN2k04kdmekekow6x_IinskeRkVcuKqC-t7j8YqQQ4QTrKQ8vb2_YCAZcMk3yAQLqVmloNwkEwDOx5Mud8huSs8AWKIU22QHFSoQKCYkPbiUh5RdHHrHUg6zxdRk19KnOLzmjg6e5s7RaDKdx5Ebb3RmlrRxtI3hxfW0WdIcUlo42i3nw1sw1PTt985C3y5saKaOemPzEBl-vO-TLW-myR18zT3yeHnxcH7N7u6vbs7P7lgjVJmZRV06waVGq33LtcaKl1DoVisB0hvECgpfSONdabhSFRaC60YJ1YBRqMUeOV772jF5is7X8xhmJi5rhHpVXT1WV4OsV9WN9NGanptkzdRH09uQfiQcoBAFL0aOr7kuPHWvIbq6CUOywfU5-GDNb_Pvv4wiXIv-sP8F-gQmv44k</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Testosterone-stimulated growth of the rat prostate may be driven by tissue hypoxia and hypoxia-inducible factor-1α</title><source>EZB-FREE-00999 freely available EZB journals</source><creator>Rudolfsson, Stina Häggström ; Bergh, Anders</creator><creatorcontrib>Rudolfsson, Stina Häggström ; Bergh, Anders</creatorcontrib><description>Testosterone-stimulated growth of the ventral prostate (VP) in castrated rats is preceded by angiogenesis, but the mechanisms coordinating vascular and tissue growth are unknown. Adult rats were castrated and some treated with testosterone. Tissue hypoxia was studied morphologically using the hypoxia marker pimonidazole (Hypoxyprobe), hypoxia-inducible factor-1 (HIF-1) α, vascular endothelial growth factor (VEGF), and carbonicanhydrase 9 (CA-9) levels by western blotting and quantitative RT-PCR. In the intact untreated prostate, most glands were unstained by the hypoxia marker but already 1 day after castration most epithelial cells in the VP were stained. Seven days after castration prostate glands were apparently normoxic again, and HIF-1α, VEGF, and CA-9 were decreased. Treatment of 7-day castrated rats with testosterone resulted in increased epithelial hypoxyprobe staining and increased HIF-1α, VEGF, and CA-9 levels. The transient increase in tissue hypoxia after testosterone treatment is probably caused by a temporary mismatch between oxygen consumption and supply. Treatment of prostate epithelial cells in vitro under normoxic conditions also increased HIF-1α, and this could be blocked if epidermal growth factor receptor (EGFR) signaling was blocked with gefitinib. In vivo gefitinib could, however, not block the testosterone induced increase in HIF-1α. Testosterone may thus induce HIF-1α and its downstream angiogenesis promoting genes by at least two mechanisms, hypoxia and EGFR signaling. Transient epithelial cell hypoxia could by rapidly increasing HIF-1α and VEGF be an essential coordinator of testosterone-stimulated vascular and glandular growth.</description><identifier>ISSN: 0022-0795</identifier><identifier>EISSN: 1479-6805</identifier><identifier>DOI: 10.1677/JOE-07-0272</identifier><identifier>PMID: 18180313</identifier><identifier>CODEN: JOENAK</identifier><language>eng</language><publisher>Colchester: BioScientifica</publisher><subject>Biological and medical sciences ; Fundamental and applied biological sciences. Psychology ; Hormone metabolism and regulation ; Mammalian male genital system ; Regular papers ; Vertebrates: reproduction</subject><ispartof>Journal of endocrinology, 2008-01, Vol.196 (1), p.11-19</ispartof><rights>2008 Society for Endocrinology</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b385t-c195e32791c9fd2991625049d98307fa11604f47afe5a288614329b838b0a8193</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20043424$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Rudolfsson, Stina Häggström</creatorcontrib><creatorcontrib>Bergh, Anders</creatorcontrib><title>Testosterone-stimulated growth of the rat prostate may be driven by tissue hypoxia and hypoxia-inducible factor-1α</title><title>Journal of endocrinology</title><description>Testosterone-stimulated growth of the ventral prostate (VP) in castrated rats is preceded by angiogenesis, but the mechanisms coordinating vascular and tissue growth are unknown. Adult rats were castrated and some treated with testosterone. Tissue hypoxia was studied morphologically using the hypoxia marker pimonidazole (Hypoxyprobe), hypoxia-inducible factor-1 (HIF-1) α, vascular endothelial growth factor (VEGF), and carbonicanhydrase 9 (CA-9) levels by western blotting and quantitative RT-PCR. In the intact untreated prostate, most glands were unstained by the hypoxia marker but already 1 day after castration most epithelial cells in the VP were stained. Seven days after castration prostate glands were apparently normoxic again, and HIF-1α, VEGF, and CA-9 were decreased. Treatment of 7-day castrated rats with testosterone resulted in increased epithelial hypoxyprobe staining and increased HIF-1α, VEGF, and CA-9 levels. The transient increase in tissue hypoxia after testosterone treatment is probably caused by a temporary mismatch between oxygen consumption and supply. Treatment of prostate epithelial cells in vitro under normoxic conditions also increased HIF-1α, and this could be blocked if epidermal growth factor receptor (EGFR) signaling was blocked with gefitinib. In vivo gefitinib could, however, not block the testosterone induced increase in HIF-1α. Testosterone may thus induce HIF-1α and its downstream angiogenesis promoting genes by at least two mechanisms, hypoxia and EGFR signaling. Transient epithelial cell hypoxia could by rapidly increasing HIF-1α and VEGF be an essential coordinator of testosterone-stimulated vascular and glandular growth.</description><subject>Biological and medical sciences</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hormone metabolism and regulation</subject><subject>Mammalian male genital system</subject><subject>Regular papers</subject><subject>Vertebrates: reproduction</subject><issn>0022-0795</issn><issn>1479-6805</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNp9kU1KBDEQhYMoOv6svEA2riRalXR3kqWIvwhudN2k04kdmekekow6x_IinskeRkVcuKqC-t7j8YqQQ4QTrKQ8vb2_YCAZcMk3yAQLqVmloNwkEwDOx5Mud8huSs8AWKIU22QHFSoQKCYkPbiUh5RdHHrHUg6zxdRk19KnOLzmjg6e5s7RaDKdx5Ebb3RmlrRxtI3hxfW0WdIcUlo42i3nw1sw1PTt985C3y5saKaOemPzEBl-vO-TLW-myR18zT3yeHnxcH7N7u6vbs7P7lgjVJmZRV06waVGq33LtcaKl1DoVisB0hvECgpfSONdabhSFRaC60YJ1YBRqMUeOV772jF5is7X8xhmJi5rhHpVXT1WV4OsV9WN9NGanptkzdRH09uQfiQcoBAFL0aOr7kuPHWvIbq6CUOywfU5-GDNb_Pvv4wiXIv-sP8F-gQmv44k</recordid><startdate>20080101</startdate><enddate>20080101</enddate><creator>Rudolfsson, Stina Häggström</creator><creator>Bergh, Anders</creator><general>BioScientifica</general><general>Portland Press</general><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20080101</creationdate><title>Testosterone-stimulated growth of the rat prostate may be driven by tissue hypoxia and hypoxia-inducible factor-1α</title><author>Rudolfsson, Stina Häggström ; Bergh, Anders</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b385t-c195e32791c9fd2991625049d98307fa11604f47afe5a288614329b838b0a8193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Biological and medical sciences</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hormone metabolism and regulation</topic><topic>Mammalian male genital system</topic><topic>Regular papers</topic><topic>Vertebrates: reproduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rudolfsson, Stina Häggström</creatorcontrib><creatorcontrib>Bergh, Anders</creatorcontrib><collection>Pascal-Francis</collection><collection>CrossRef</collection><jtitle>Journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rudolfsson, Stina Häggström</au><au>Bergh, Anders</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Testosterone-stimulated growth of the rat prostate may be driven by tissue hypoxia and hypoxia-inducible factor-1α</atitle><jtitle>Journal of endocrinology</jtitle><date>2008-01-01</date><risdate>2008</risdate><volume>196</volume><issue>1</issue><spage>11</spage><epage>19</epage><pages>11-19</pages><issn>0022-0795</issn><eissn>1479-6805</eissn><coden>JOENAK</coden><abstract>Testosterone-stimulated growth of the ventral prostate (VP) in castrated rats is preceded by angiogenesis, but the mechanisms coordinating vascular and tissue growth are unknown. Adult rats were castrated and some treated with testosterone. Tissue hypoxia was studied morphologically using the hypoxia marker pimonidazole (Hypoxyprobe), hypoxia-inducible factor-1 (HIF-1) α, vascular endothelial growth factor (VEGF), and carbonicanhydrase 9 (CA-9) levels by western blotting and quantitative RT-PCR. In the intact untreated prostate, most glands were unstained by the hypoxia marker but already 1 day after castration most epithelial cells in the VP were stained. Seven days after castration prostate glands were apparently normoxic again, and HIF-1α, VEGF, and CA-9 were decreased. Treatment of 7-day castrated rats with testosterone resulted in increased epithelial hypoxyprobe staining and increased HIF-1α, VEGF, and CA-9 levels. The transient increase in tissue hypoxia after testosterone treatment is probably caused by a temporary mismatch between oxygen consumption and supply. Treatment of prostate epithelial cells in vitro under normoxic conditions also increased HIF-1α, and this could be blocked if epidermal growth factor receptor (EGFR) signaling was blocked with gefitinib. In vivo gefitinib could, however, not block the testosterone induced increase in HIF-1α. Testosterone may thus induce HIF-1α and its downstream angiogenesis promoting genes by at least two mechanisms, hypoxia and EGFR signaling. Transient epithelial cell hypoxia could by rapidly increasing HIF-1α and VEGF be an essential coordinator of testosterone-stimulated vascular and glandular growth.</abstract><cop>Colchester</cop><pub>BioScientifica</pub><pmid>18180313</pmid><doi>10.1677/JOE-07-0272</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0022-0795
ispartof Journal of endocrinology, 2008-01, Vol.196 (1), p.11-19
issn 0022-0795
1479-6805
language eng
recordid cdi_crossref_primary_10_1677_JOE_07_0272
source EZB-FREE-00999 freely available EZB journals
subjects Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Hormone metabolism and regulation
Mammalian male genital system
Regular papers
Vertebrates: reproduction
title Testosterone-stimulated growth of the rat prostate may be driven by tissue hypoxia and hypoxia-inducible factor-1α
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T20%3A53%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pascalfrancis_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Testosterone-stimulated%20growth%20of%20the%20rat%20prostate%20may%20be%20driven%20by%20tissue%20hypoxia%20and%20hypoxia-inducible%20factor-1%CE%B1&rft.jtitle=Journal%20of%20endocrinology&rft.au=Rudolfsson,%20Stina%20H%C3%A4ggstr%C3%B6m&rft.date=2008-01-01&rft.volume=196&rft.issue=1&rft.spage=11&rft.epage=19&rft.pages=11-19&rft.issn=0022-0795&rft.eissn=1479-6805&rft.coden=JOENAK&rft_id=info:doi/10.1677/JOE-07-0272&rft_dat=%3Cpascalfrancis_cross%3E20043424%3C/pascalfrancis_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/18180313&rfr_iscdi=true