Cyclooxygenase-2 and Prostaglandin F2α in Syrian Hamster Leydig Cells: Inhibitory Role on Luteinizing Hormone/Human Chorionic Gonadotropin-Stimulated Testosterone Production
We have previously found that cyclooxygenase-2 (COX-2), a key enzyme in the biosynthesis of prostaglandins (PGs), is present in the testicular interstitial cells of infertile men, whereas it is absent in human testes with no evident morphological changes or abnormalities. To find an animal model for...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2006-09, Vol.147 (9), p.4476-4485 |
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| creator | Frungieri, Mónica B Gonzalez-Calvar, Silvia I Parborell, Fernanda Albrecht, Martin Mayerhofer, Artur Calandra, Ricardo S |
| description | We have previously found that cyclooxygenase-2 (COX-2), a key enzyme in the biosynthesis of prostaglandins (PGs), is present in the testicular interstitial cells of infertile men, whereas it is absent in human testes with no evident morphological changes or abnormalities. To find an animal model for further investigating COX-2 and its role in testicular steroidogenesis, we screened testes from adult species ranging from mice to monkeys. By using immunohistochemical assays, we found COX-2 expression only in Leydig cells of the reproductively active (peripubertal, pubertal, and adult) seasonal breeder Syrian hamster. COX-2 expression in hamster Leydig cells was confirmed by RT-PCR. In contrast, COX-1 expression was not detected in hamster testes. Because COX-2 expression implies PG synthesis, we investigated the effect of various PGs on testosterone production and found that PGF2α stood out because it significantly reduced human chorionic gonadotropin-stimulated testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular steroidogenic acute regulatory protein and 17β-hydroxysteroid dehydrogenase. Testicular concentration and content of PGF2α in reproductively active hamsters as well as production of PGF2α from isolated hamster Leydig cells were also determined. Moreover, PGF2α receptors were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only and germ arrest syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2α production, PGF2α receptors, steroidogenic acute regulatory protein, and 17β-hydroxysteroid dehydrogenase represents a physiological local inhibitory system of human chorionic gonadotropin-stimulated testosterone production in the Syrian hamster testes. |
| doi_str_mv | 10.1210/en.2006-0090 |
| format | Article |
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To find an animal model for further investigating COX-2 and its role in testicular steroidogenesis, we screened testes from adult species ranging from mice to monkeys. By using immunohistochemical assays, we found COX-2 expression only in Leydig cells of the reproductively active (peripubertal, pubertal, and adult) seasonal breeder Syrian hamster. COX-2 expression in hamster Leydig cells was confirmed by RT-PCR. In contrast, COX-1 expression was not detected in hamster testes. Because COX-2 expression implies PG synthesis, we investigated the effect of various PGs on testosterone production and found that PGF2α stood out because it significantly reduced human chorionic gonadotropin-stimulated testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular steroidogenic acute regulatory protein and 17β-hydroxysteroid dehydrogenase. Testicular concentration and content of PGF2α in reproductively active hamsters as well as production of PGF2α from isolated hamster Leydig cells were also determined. Moreover, PGF2α receptors were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only and germ arrest syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2α production, PGF2α receptors, steroidogenic acute regulatory protein, and 17β-hydroxysteroid dehydrogenase represents a physiological local inhibitory system of human chorionic gonadotropin-stimulated testosterone production in the Syrian hamster testes.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2006-0090</identifier><identifier>PMID: 16740978</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>17-Hydroxysteroid Dehydrogenases - genetics ; Abnormalities ; Adult ; Animal models ; Animals ; Biological and medical sciences ; Biopsy ; Biosynthesis ; Chorionic gonadotropin ; Chorionic Gonadotropin - pharmacology ; Cricetinae ; Cyclooxygenase 1 - analysis ; Cyclooxygenase 2 - analysis ; Cyclooxygenase 2 - genetics ; Cyclooxygenase 2 - physiology ; Cyclooxygenase-1 ; Cyclooxygenase-2 ; Dehydrogenase ; Dehydrogenases ; Dinoprost - analysis ; Dinoprost - pharmacology ; Dinoprost - physiology ; Fundamental and applied biological sciences. Psychology ; Gene Expression - drug effects ; Gonadotropins ; Hamsters ; Humans ; Hydroxysteroids ; Immunohistochemistry ; Interstitial cells ; Leydig cells ; Leydig Cells - chemistry ; Leydig Cells - drug effects ; Leydig Cells - metabolism ; Luteinizing hormone ; Luteinizing Hormone - pharmacology ; Male ; Mesocricetus ; Phosphoproteins - genetics ; Pituitary (anterior) ; Prostaglandin F2a ; Prostaglandins ; Proteins ; Receptors ; Receptors, Prostaglandin - analysis ; Receptors, Prostaglandin - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; Steroidogenesis ; Steroidogenic acute regulatory protein ; Testes ; Testis - chemistry ; Testis - enzymology ; Testosterone ; Testosterone - biosynthesis ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2006-09, Vol.147 (9), p.4476-4485</ispartof><rights>Copyright © 2006 by The Endocrine Society 2006</rights><rights>2006 INIST-CNRS</rights><rights>Copyright © 2006 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c461t-3e4a02c40fcdd988642faed60465f1e352318106cbf6f002c3e2a9e4ed0e95923</citedby><cites>FETCH-LOGICAL-c461t-3e4a02c40fcdd988642faed60465f1e352318106cbf6f002c3e2a9e4ed0e95923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18043289$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16740978$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Frungieri, Mónica B</creatorcontrib><creatorcontrib>Gonzalez-Calvar, Silvia I</creatorcontrib><creatorcontrib>Parborell, Fernanda</creatorcontrib><creatorcontrib>Albrecht, Martin</creatorcontrib><creatorcontrib>Mayerhofer, Artur</creatorcontrib><creatorcontrib>Calandra, Ricardo S</creatorcontrib><title>Cyclooxygenase-2 and Prostaglandin F2α in Syrian Hamster Leydig Cells: Inhibitory Role on Luteinizing Hormone/Human Chorionic Gonadotropin-Stimulated Testosterone Production</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>We have previously found that cyclooxygenase-2 (COX-2), a key enzyme in the biosynthesis of prostaglandins (PGs), is present in the testicular interstitial cells of infertile men, whereas it is absent in human testes with no evident morphological changes or abnormalities. To find an animal model for further investigating COX-2 and its role in testicular steroidogenesis, we screened testes from adult species ranging from mice to monkeys. By using immunohistochemical assays, we found COX-2 expression only in Leydig cells of the reproductively active (peripubertal, pubertal, and adult) seasonal breeder Syrian hamster. COX-2 expression in hamster Leydig cells was confirmed by RT-PCR. In contrast, COX-1 expression was not detected in hamster testes. Because COX-2 expression implies PG synthesis, we investigated the effect of various PGs on testosterone production and found that PGF2α stood out because it significantly reduced human chorionic gonadotropin-stimulated testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular steroidogenic acute regulatory protein and 17β-hydroxysteroid dehydrogenase. Testicular concentration and content of PGF2α in reproductively active hamsters as well as production of PGF2α from isolated hamster Leydig cells were also determined. Moreover, PGF2α receptors were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only and germ arrest syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2α production, PGF2α receptors, steroidogenic acute regulatory protein, and 17β-hydroxysteroid dehydrogenase represents a physiological local inhibitory system of human chorionic gonadotropin-stimulated testosterone production in the Syrian hamster testes.</description><subject>17-Hydroxysteroid Dehydrogenases - genetics</subject><subject>Abnormalities</subject><subject>Adult</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Biosynthesis</subject><subject>Chorionic gonadotropin</subject><subject>Chorionic Gonadotropin - pharmacology</subject><subject>Cricetinae</subject><subject>Cyclooxygenase 1 - analysis</subject><subject>Cyclooxygenase 2 - analysis</subject><subject>Cyclooxygenase 2 - genetics</subject><subject>Cyclooxygenase 2 - physiology</subject><subject>Cyclooxygenase-1</subject><subject>Cyclooxygenase-2</subject><subject>Dehydrogenase</subject><subject>Dehydrogenases</subject><subject>Dinoprost - analysis</subject><subject>Dinoprost - pharmacology</subject><subject>Dinoprost - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression - drug effects</subject><subject>Gonadotropins</subject><subject>Hamsters</subject><subject>Humans</subject><subject>Hydroxysteroids</subject><subject>Immunohistochemistry</subject><subject>Interstitial cells</subject><subject>Leydig cells</subject><subject>Leydig Cells - chemistry</subject><subject>Leydig Cells - drug effects</subject><subject>Leydig Cells - metabolism</subject><subject>Luteinizing hormone</subject><subject>Luteinizing Hormone - pharmacology</subject><subject>Male</subject><subject>Mesocricetus</subject><subject>Phosphoproteins - genetics</subject><subject>Pituitary (anterior)</subject><subject>Prostaglandin F2a</subject><subject>Prostaglandins</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Receptors, Prostaglandin - analysis</subject><subject>Receptors, Prostaglandin - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Steroidogenesis</subject><subject>Steroidogenic acute regulatory protein</subject><subject>Testes</subject><subject>Testis - chemistry</subject><subject>Testis - enzymology</subject><subject>Testosterone</subject><subject>Testosterone - biosynthesis</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU-L1TAUxYsoznN051oCIm7szM2f_pudFGfewAPFGdclL7l9k6FNatKC9UMJfhE_kymv8Da6ugn87jknOUnymsIFZRQu0V4wgDwFqOBJsqGVyNKCFvA02QBQnhaMFWfJixAe41UIwZ8nZzQvBFRFuUl-1bPqnPsxH9DKgCkj0mryxbswykMXz8aSa_bnN4nzbvZGWrKVfRjRkx3O2hxIjV0XrsitfTB7Mzo_k6-uQ-Is2U0jGmt-GnsgW-d7Z_FyO_VRon5w3jhrFLlxVmo3ejcYm96Npp86OaIm9xhGt9jEpSWOntQYN14mz1rZBXy1zvPk2_Wn-3qb7j7f3NYfd6kSOR1TjkICUwJapXVVlrlgrUSdg8izliLPGKclhVzt27yFSHJkskKBGrDKKsbPk7dH3cG771PM0jy6ydto2XDKIaugohCpD0dKxf8KHttm8KaXfm4oNEs5DdpmKadZyon4m1V02veoT_DaRgTerYAMSnatl1aZcOJKEJyVVeTeHzk3Df-zTFdLfiTRaqe8sTh4DOH0mn8G_QvnqLft</recordid><startdate>20060901</startdate><enddate>20060901</enddate><creator>Frungieri, Mónica B</creator><creator>Gonzalez-Calvar, Silvia I</creator><creator>Parborell, Fernanda</creator><creator>Albrecht, Martin</creator><creator>Mayerhofer, Artur</creator><creator>Calandra, Ricardo S</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></search><sort><creationdate>20060901</creationdate><title>Cyclooxygenase-2 and Prostaglandin F2α in Syrian Hamster Leydig Cells: Inhibitory Role on Luteinizing Hormone/Human Chorionic Gonadotropin-Stimulated Testosterone Production</title><author>Frungieri, Mónica B ; Gonzalez-Calvar, Silvia I ; Parborell, Fernanda ; Albrecht, Martin ; Mayerhofer, Artur ; Calandra, Ricardo S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c461t-3e4a02c40fcdd988642faed60465f1e352318106cbf6f002c3e2a9e4ed0e95923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>17-Hydroxysteroid Dehydrogenases - genetics</topic><topic>Abnormalities</topic><topic>Adult</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Biosynthesis</topic><topic>Chorionic gonadotropin</topic><topic>Chorionic Gonadotropin - pharmacology</topic><topic>Cricetinae</topic><topic>Cyclooxygenase 1 - analysis</topic><topic>Cyclooxygenase 2 - analysis</topic><topic>Cyclooxygenase 2 - genetics</topic><topic>Cyclooxygenase 2 - physiology</topic><topic>Cyclooxygenase-1</topic><topic>Cyclooxygenase-2</topic><topic>Dehydrogenase</topic><topic>Dehydrogenases</topic><topic>Dinoprost - analysis</topic><topic>Dinoprost - pharmacology</topic><topic>Dinoprost - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression - drug effects</topic><topic>Gonadotropins</topic><topic>Hamsters</topic><topic>Humans</topic><topic>Hydroxysteroids</topic><topic>Immunohistochemistry</topic><topic>Interstitial cells</topic><topic>Leydig cells</topic><topic>Leydig Cells - chemistry</topic><topic>Leydig Cells - drug effects</topic><topic>Leydig Cells - metabolism</topic><topic>Luteinizing hormone</topic><topic>Luteinizing Hormone - pharmacology</topic><topic>Male</topic><topic>Mesocricetus</topic><topic>Phosphoproteins - genetics</topic><topic>Pituitary (anterior)</topic><topic>Prostaglandin F2a</topic><topic>Prostaglandins</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Receptors, Prostaglandin - analysis</topic><topic>Receptors, Prostaglandin - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Steroidogenesis</topic><topic>Steroidogenic acute regulatory protein</topic><topic>Testes</topic><topic>Testis - chemistry</topic><topic>Testis - enzymology</topic><topic>Testosterone</topic><topic>Testosterone - biosynthesis</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Frungieri, Mónica B</creatorcontrib><creatorcontrib>Gonzalez-Calvar, Silvia I</creatorcontrib><creatorcontrib>Parborell, Fernanda</creatorcontrib><creatorcontrib>Albrecht, Martin</creatorcontrib><creatorcontrib>Mayerhofer, Artur</creatorcontrib><creatorcontrib>Calandra, Ricardo S</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><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Frungieri, Mónica B</au><au>Gonzalez-Calvar, Silvia I</au><au>Parborell, Fernanda</au><au>Albrecht, Martin</au><au>Mayerhofer, Artur</au><au>Calandra, Ricardo S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cyclooxygenase-2 and Prostaglandin F2α in Syrian Hamster Leydig Cells: Inhibitory Role on Luteinizing Hormone/Human Chorionic Gonadotropin-Stimulated Testosterone Production</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2006-09-01</date><risdate>2006</risdate><volume>147</volume><issue>9</issue><spage>4476</spage><epage>4485</epage><pages>4476-4485</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>We have previously found that cyclooxygenase-2 (COX-2), a key enzyme in the biosynthesis of prostaglandins (PGs), is present in the testicular interstitial cells of infertile men, whereas it is absent in human testes with no evident morphological changes or abnormalities. To find an animal model for further investigating COX-2 and its role in testicular steroidogenesis, we screened testes from adult species ranging from mice to monkeys. By using immunohistochemical assays, we found COX-2 expression only in Leydig cells of the reproductively active (peripubertal, pubertal, and adult) seasonal breeder Syrian hamster. COX-2 expression in hamster Leydig cells was confirmed by RT-PCR. In contrast, COX-1 expression was not detected in hamster testes. Because COX-2 expression implies PG synthesis, we investigated the effect of various PGs on testosterone production and found that PGF2α stood out because it significantly reduced human chorionic gonadotropin-stimulated testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular steroidogenic acute regulatory protein and 17β-hydroxysteroid dehydrogenase. Testicular concentration and content of PGF2α in reproductively active hamsters as well as production of PGF2α from isolated hamster Leydig cells were also determined. Moreover, PGF2α receptors were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only and germ arrest syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2α production, PGF2α receptors, steroidogenic acute regulatory protein, and 17β-hydroxysteroid dehydrogenase represents a physiological local inhibitory system of human chorionic gonadotropin-stimulated testosterone production in the Syrian hamster testes.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>16740978</pmid><doi>10.1210/en.2006-0090</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 17-Hydroxysteroid Dehydrogenases - genetics Abnormalities Adult Animal models Animals Biological and medical sciences Biopsy Biosynthesis Chorionic gonadotropin Chorionic Gonadotropin - pharmacology Cricetinae Cyclooxygenase 1 - analysis Cyclooxygenase 2 - analysis Cyclooxygenase 2 - genetics Cyclooxygenase 2 - physiology Cyclooxygenase-1 Cyclooxygenase-2 Dehydrogenase Dehydrogenases Dinoprost - analysis Dinoprost - pharmacology Dinoprost - physiology Fundamental and applied biological sciences. Psychology Gene Expression - drug effects Gonadotropins Hamsters Humans Hydroxysteroids Immunohistochemistry Interstitial cells Leydig cells Leydig Cells - chemistry Leydig Cells - drug effects Leydig Cells - metabolism Luteinizing hormone Luteinizing Hormone - pharmacology Male Mesocricetus Phosphoproteins - genetics Pituitary (anterior) Prostaglandin F2a Prostaglandins Proteins Receptors Receptors, Prostaglandin - analysis Receptors, Prostaglandin - genetics Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Steroidogenesis Steroidogenic acute regulatory protein Testes Testis - chemistry Testis - enzymology Testosterone Testosterone - biosynthesis Vertebrates: endocrinology |
| title | Cyclooxygenase-2 and Prostaglandin F2α in Syrian Hamster Leydig Cells: Inhibitory Role on Luteinizing Hormone/Human Chorionic Gonadotropin-Stimulated Testosterone Production |
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