Ghrelin Inhibits the Proliferative Activity of Immature Leydig Cells in Vivo and Regulates Stem Cell Factor Messenger Ribonucleic Acid Expression in Rat Testis
Ghrelin has emerged as putative regulator of an array of endocrine and nonendocrine functions, including cell proliferation. Recently, we provided evidence for the expression of ghrelin in mature, but not in undifferentiated, Leydig cells of rat and human testis. Yet testicular actions of ghrelin, o...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2004-11, Vol.145 (11), p.4825-4834 |
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| creator | Barreiro, M. L Gaytan, F Castellano, J. M Suominen, J. S Roa, J Gaytan, M Aguilar, E Dieguez, C Toppari, J Tena-Sempere, M |
| description | Ghrelin has emerged as putative regulator of an array of endocrine and nonendocrine functions, including cell proliferation. Recently, we provided evidence for the expression of ghrelin in mature, but not in undifferentiated, Leydig cells of rat and human testis. Yet testicular actions of ghrelin, other than modulation of testosterone secretion, remain unexplored. In the present study we evaluated the effects of ghrelin on proliferation of Leydig cell precursors during puberty and after selective elimination of mature Leydig cells by treatment with ethylene dimethane sulfonate. In these settings, intratesticular injection of ghrelin significantly decreased the proliferative activity of differentiating immature Leydig cells, estimated by 5-bromodeoxyuridine labeling. This response was selective and associated, in ethylene dimethane sulfonate-treated animals, with a decrease in the mRNA levels of stem cell factor (SCF), i.e. a key signal in spermatogenesis and a putative regulator of Leydig cell development. Thus, the effects of ghrelin on SCF gene expression were evaluated. In adult rats, ghrelin induced a significant decrease in SCF mRNA levels in vivo. Such an inhibitory action was also detected in vitro using cultures of staged seminiferous tubules. The inhibitory effect of ghrelin in vivo was dependent on proper FSH input, because it was detected in hypophysectomized rats only after FSH replacement. Overall, it is proposed that acquisition of ghrelin expression by Leydig cell precursors during differentiation may operate as a self-regulatory signal for the inhibition of the proliferative activity of this cell type through direct or indirect (i.e. SCF-mediated) mechanisms. In addition, we present novel evidence for the ability of ghrelin to modulate the expression of the SCF gene, which may have implications for the mode of action of this molecule in the testis as well as in other physiological systems. |
| doi_str_mv | 10.1210/en.2004-0732 |
| format | Article |
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L ; Gaytan, F ; Castellano, J. M ; Suominen, J. S ; Roa, J ; Gaytan, M ; Aguilar, E ; Dieguez, C ; Toppari, J ; Tena-Sempere, M</creator><creatorcontrib>Barreiro, M. L ; Gaytan, F ; Castellano, J. M ; Suominen, J. S ; Roa, J ; Gaytan, M ; Aguilar, E ; Dieguez, C ; Toppari, J ; Tena-Sempere, M</creatorcontrib><description>Ghrelin has emerged as putative regulator of an array of endocrine and nonendocrine functions, including cell proliferation. Recently, we provided evidence for the expression of ghrelin in mature, but not in undifferentiated, Leydig cells of rat and human testis. Yet testicular actions of ghrelin, other than modulation of testosterone secretion, remain unexplored. In the present study we evaluated the effects of ghrelin on proliferation of Leydig cell precursors during puberty and after selective elimination of mature Leydig cells by treatment with ethylene dimethane sulfonate. In these settings, intratesticular injection of ghrelin significantly decreased the proliferative activity of differentiating immature Leydig cells, estimated by 5-bromodeoxyuridine labeling. This response was selective and associated, in ethylene dimethane sulfonate-treated animals, with a decrease in the mRNA levels of stem cell factor (SCF), i.e. a key signal in spermatogenesis and a putative regulator of Leydig cell development. Thus, the effects of ghrelin on SCF gene expression were evaluated. In adult rats, ghrelin induced a significant decrease in SCF mRNA levels in vivo. Such an inhibitory action was also detected in vitro using cultures of staged seminiferous tubules. The inhibitory effect of ghrelin in vivo was dependent on proper FSH input, because it was detected in hypophysectomized rats only after FSH replacement. Overall, it is proposed that acquisition of ghrelin expression by Leydig cell precursors during differentiation may operate as a self-regulatory signal for the inhibition of the proliferative activity of this cell type through direct or indirect (i.e. SCF-mediated) mechanisms. In addition, we present novel evidence for the ability of ghrelin to modulate the expression of the SCF gene, which may have implications for the mode of action of this molecule in the testis as well as in other physiological systems.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2004-0732</identifier><identifier>PMID: 15284210</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Age Factors ; Animals ; Biological and medical sciences ; Bromodeoxyuridine ; Cell differentiation ; Cell Differentiation - drug effects ; Cell Differentiation - physiology ; Cell Division - drug effects ; Cell Division - physiology ; Cell proliferation ; Ethylene ; Follicle-stimulating hormone ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression - drug effects ; Gene Expression - physiology ; Ghrelin ; In vivo methods and tests ; Leydig cells ; Leydig Cells - cytology ; Leydig Cells - drug effects ; Leydig Cells - physiology ; Male ; Mode of action ; Peptide Hormones - pharmacology ; Precursors ; Puberty ; Rats ; Rats, Wistar ; RNA, Messenger - metabolism ; Spermatogenesis ; Stem cell factor ; Stem Cell Factor - genetics ; Stem cells ; Sulfonates ; Testes ; Testis - cytology ; Testis - physiology ; Testosterone ; Tubules ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2004-11, Vol.145 (11), p.4825-4834</ispartof><rights>Copyright © 2004 by The Endocrine Society 2004</rights><rights>2004 INIST-CNRS</rights><rights>Copyright © 2004 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-592577b71b94acd6c2f2d0cf62c724395e14045b81facd3fdf166c210c9e97063</citedby><cites>FETCH-LOGICAL-c459t-592577b71b94acd6c2f2d0cf62c724395e14045b81facd3fdf166c210c9e97063</cites></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&idt=16215394$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15284210$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barreiro, M. L</creatorcontrib><creatorcontrib>Gaytan, F</creatorcontrib><creatorcontrib>Castellano, J. M</creatorcontrib><creatorcontrib>Suominen, J. S</creatorcontrib><creatorcontrib>Roa, J</creatorcontrib><creatorcontrib>Gaytan, M</creatorcontrib><creatorcontrib>Aguilar, E</creatorcontrib><creatorcontrib>Dieguez, C</creatorcontrib><creatorcontrib>Toppari, J</creatorcontrib><creatorcontrib>Tena-Sempere, M</creatorcontrib><title>Ghrelin Inhibits the Proliferative Activity of Immature Leydig Cells in Vivo and Regulates Stem Cell Factor Messenger Ribonucleic Acid Expression in Rat Testis</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Ghrelin has emerged as putative regulator of an array of endocrine and nonendocrine functions, including cell proliferation. Recently, we provided evidence for the expression of ghrelin in mature, but not in undifferentiated, Leydig cells of rat and human testis. Yet testicular actions of ghrelin, other than modulation of testosterone secretion, remain unexplored. In the present study we evaluated the effects of ghrelin on proliferation of Leydig cell precursors during puberty and after selective elimination of mature Leydig cells by treatment with ethylene dimethane sulfonate. In these settings, intratesticular injection of ghrelin significantly decreased the proliferative activity of differentiating immature Leydig cells, estimated by 5-bromodeoxyuridine labeling. This response was selective and associated, in ethylene dimethane sulfonate-treated animals, with a decrease in the mRNA levels of stem cell factor (SCF), i.e. a key signal in spermatogenesis and a putative regulator of Leydig cell development. Thus, the effects of ghrelin on SCF gene expression were evaluated. In adult rats, ghrelin induced a significant decrease in SCF mRNA levels in vivo. Such an inhibitory action was also detected in vitro using cultures of staged seminiferous tubules. The inhibitory effect of ghrelin in vivo was dependent on proper FSH input, because it was detected in hypophysectomized rats only after FSH replacement. Overall, it is proposed that acquisition of ghrelin expression by Leydig cell precursors during differentiation may operate as a self-regulatory signal for the inhibition of the proliferative activity of this cell type through direct or indirect (i.e. SCF-mediated) mechanisms. In addition, we present novel evidence for the ability of ghrelin to modulate the expression of the SCF gene, which may have implications for the mode of action of this molecule in the testis as well as in other physiological systems.</description><subject>Age Factors</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bromodeoxyuridine</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Division - drug effects</subject><subject>Cell Division - physiology</subject><subject>Cell proliferation</subject><subject>Ethylene</subject><subject>Follicle-stimulating hormone</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression - physiology</subject><subject>Ghrelin</subject><subject>In vivo methods and tests</subject><subject>Leydig cells</subject><subject>Leydig Cells - cytology</subject><subject>Leydig Cells - drug effects</subject><subject>Leydig Cells - physiology</subject><subject>Male</subject><subject>Mode of action</subject><subject>Peptide Hormones - pharmacology</subject><subject>Precursors</subject><subject>Puberty</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA, Messenger - metabolism</subject><subject>Spermatogenesis</subject><subject>Stem cell factor</subject><subject>Stem Cell Factor - genetics</subject><subject>Stem cells</subject><subject>Sulfonates</subject><subject>Testes</subject><subject>Testis - cytology</subject><subject>Testis - physiology</subject><subject>Testosterone</subject><subject>Tubules</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV-LEzEUxYMobq2--SwBUV-cNf9m0nlcyu5aqCh19XXIZG7aLDNJN8ks9tPsV910WyiIPl3C_d1zTjgIvaXknDJKvoA7Z4SIgkjOnqEJrUVZSCrJczQhhPJCMibP0KsYb_NTCMFfojNaspnIxxP0cL0J0FuHF25jW5siThvAP4LvrYGgkr0HfKHzsGmHvcGLYVBpDICXsOvsGs-h7yPO97_tvcfKdXgF67FXCSL-mWB4AvCV0skH_A1iBLeGgFe29W7UPVid5W2HL_9sQ95a7_ZiK5XwDcRk42v0wqg-wpvjnKJfV5c386_F8vv1Yn6xLLQo61SUNSulbCVta6F0V2lmWEe0qZiWTPC6BCqIKNsZNXnNTWdolSFKdA21JBWfoo8H3W3wd2O2bgYbdc6uHPgxNlVVyzJbZfD9X-CtH4PL2RpOOSl5Nctzij4fKB18jAFMsw12UGHXUNLsa2vANfvamn1tGX93FB3bAboTfOwpAx-OgIpa9SYop208cRWjJa9F5j4dOD9u_2dZHC35gQTXeR2sg6cCTr_5Z9BHWcK9cQ</recordid><startdate>20041101</startdate><enddate>20041101</enddate><creator>Barreiro, M. 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Psychology</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression - physiology</topic><topic>Ghrelin</topic><topic>In vivo methods and tests</topic><topic>Leydig cells</topic><topic>Leydig Cells - cytology</topic><topic>Leydig Cells - drug effects</topic><topic>Leydig Cells - physiology</topic><topic>Male</topic><topic>Mode of action</topic><topic>Peptide Hormones - pharmacology</topic><topic>Precursors</topic><topic>Puberty</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>RNA, Messenger - metabolism</topic><topic>Spermatogenesis</topic><topic>Stem cell factor</topic><topic>Stem Cell Factor - genetics</topic><topic>Stem cells</topic><topic>Sulfonates</topic><topic>Testes</topic><topic>Testis - cytology</topic><topic>Testis - physiology</topic><topic>Testosterone</topic><topic>Tubules</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barreiro, M. 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L</au><au>Gaytan, F</au><au>Castellano, J. M</au><au>Suominen, J. S</au><au>Roa, J</au><au>Gaytan, M</au><au>Aguilar, E</au><au>Dieguez, C</au><au>Toppari, J</au><au>Tena-Sempere, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ghrelin Inhibits the Proliferative Activity of Immature Leydig Cells in Vivo and Regulates Stem Cell Factor Messenger Ribonucleic Acid Expression in Rat Testis</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2004-11-01</date><risdate>2004</risdate><volume>145</volume><issue>11</issue><spage>4825</spage><epage>4834</epage><pages>4825-4834</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Ghrelin has emerged as putative regulator of an array of endocrine and nonendocrine functions, including cell proliferation. Recently, we provided evidence for the expression of ghrelin in mature, but not in undifferentiated, Leydig cells of rat and human testis. Yet testicular actions of ghrelin, other than modulation of testosterone secretion, remain unexplored. In the present study we evaluated the effects of ghrelin on proliferation of Leydig cell precursors during puberty and after selective elimination of mature Leydig cells by treatment with ethylene dimethane sulfonate. In these settings, intratesticular injection of ghrelin significantly decreased the proliferative activity of differentiating immature Leydig cells, estimated by 5-bromodeoxyuridine labeling. This response was selective and associated, in ethylene dimethane sulfonate-treated animals, with a decrease in the mRNA levels of stem cell factor (SCF), i.e. a key signal in spermatogenesis and a putative regulator of Leydig cell development. Thus, the effects of ghrelin on SCF gene expression were evaluated. In adult rats, ghrelin induced a significant decrease in SCF mRNA levels in vivo. Such an inhibitory action was also detected in vitro using cultures of staged seminiferous tubules. The inhibitory effect of ghrelin in vivo was dependent on proper FSH input, because it was detected in hypophysectomized rats only after FSH replacement. Overall, it is proposed that acquisition of ghrelin expression by Leydig cell precursors during differentiation may operate as a self-regulatory signal for the inhibition of the proliferative activity of this cell type through direct or indirect (i.e. SCF-mediated) mechanisms. In addition, we present novel evidence for the ability of ghrelin to modulate the expression of the SCF gene, which may have implications for the mode of action of this molecule in the testis as well as in other physiological systems.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>15284210</pmid><doi>10.1210/en.2004-0732</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Age Factors Animals Biological and medical sciences Bromodeoxyuridine Cell differentiation Cell Differentiation - drug effects Cell Differentiation - physiology Cell Division - drug effects Cell Division - physiology Cell proliferation Ethylene Follicle-stimulating hormone Fundamental and applied biological sciences. Psychology Gene expression Gene Expression - drug effects Gene Expression - physiology Ghrelin In vivo methods and tests Leydig cells Leydig Cells - cytology Leydig Cells - drug effects Leydig Cells - physiology Male Mode of action Peptide Hormones - pharmacology Precursors Puberty Rats Rats, Wistar RNA, Messenger - metabolism Spermatogenesis Stem cell factor Stem Cell Factor - genetics Stem cells Sulfonates Testes Testis - cytology Testis - physiology Testosterone Tubules Vertebrates: endocrinology |
| title | Ghrelin Inhibits the Proliferative Activity of Immature Leydig Cells in Vivo and Regulates Stem Cell Factor Messenger Ribonucleic Acid Expression in Rat Testis |
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