Steroid production in the thymus : implications for thymocyte selection
The mouse thymus was assessed for its ability to produce steroids. Cultured thymic non-T cells produced soluble pregnenolone and deoxycorticosterone, and immunohistochemistry demonstrated steroidogenic enzymes in radioresistant thymic epithelial cells but not in thymocytes. Inhibition of thymic cort...
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| Veröffentlicht in: | The Journal of experimental medicine 1994-06, Vol.179 (6), p.1835-1846 |
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| container_end_page | 1846 |
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| container_issue | 6 |
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| container_title | The Journal of experimental medicine |
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| creator | VACCHIO, M. S PAPADOPOULOS, V ASHWELL, J. D |
| description | The mouse thymus was assessed for its ability to produce steroids. Cultured thymic non-T cells produced soluble pregnenolone and deoxycorticosterone, and immunohistochemistry demonstrated steroidogenic enzymes in radioresistant thymic epithelial cells but not in thymocytes. Inhibition of thymic corticosterone production or blockade of the glucocorticoid receptor with RU-486 resulted in enhanced TCR-mediated, antigen-specific deletion of immature thymocytes. These data indicate that locally produced glucocorticoids, because of their antagonism of TCR-mediated signaling for death, may be a key element of antigen-specific thymocyte selection. |
| doi_str_mv | 10.1084/jem.179.6.1835 |
| format | Article |
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These data indicate that locally produced glucocorticoids, because of their antagonism of TCR-mediated signaling for death, may be a key element of antigen-specific thymocyte selection.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.179.6.1835</identifier><identifier>PMID: 8195711</identifier><identifier>CODEN: JEMEAV</identifier><language>eng</language><publisher>New York, NY: Rockefeller University Press</publisher><subject>Aging - physiology ; Animals ; Biological and medical sciences ; Cells, Cultured ; Cholesterol Side-Chain Cleavage Enzyme - biosynthesis ; Corticosterone - biosynthesis ; Corticosterone - pharmacology ; Cytochrome P-450 Enzyme System - metabolism ; Desoxycorticosterone - biosynthesis ; Epithelial Cells ; Epithelium - metabolism ; Epithelium - radiation effects ; Fetus ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Immunobiology ; Lymphocyte Depletion ; Lymphoid organs: ontogeny, organization, homing phenomenon ; Metyrapone - pharmacology ; Mice ; Mice, Inbred BALB C ; Mifepristone - pharmacology ; Organ Culture Techniques ; Pregnenolone - biosynthesis ; Receptors, Antigen, T-Cell - drug effects ; Receptors, Antigen, T-Cell - physiology ; Receptors, Glucocorticoid - drug effects ; Receptors, Glucocorticoid - physiology ; Signal Transduction ; T-Lymphocytes - cytology ; T-Lymphocytes - drug effects ; T-Lymphocytes - metabolism ; Thymus Gland - cytology ; Thymus Gland - growth & development ; Thymus Gland - metabolism</subject><ispartof>The Journal of experimental medicine, 1994-06, Vol.179 (6), p.1835-1846</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-d87a313a220a7ae760c9af059ff16292c5881526a62ae9765bb3020907bdcef53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4151650$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8195711$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VACCHIO, M. S</creatorcontrib><creatorcontrib>PAPADOPOULOS, V</creatorcontrib><creatorcontrib>ASHWELL, J. D</creatorcontrib><title>Steroid production in the thymus : implications for thymocyte selection</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>The mouse thymus was assessed for its ability to produce steroids. Cultured thymic non-T cells produced soluble pregnenolone and deoxycorticosterone, and immunohistochemistry demonstrated steroidogenic enzymes in radioresistant thymic epithelial cells but not in thymocytes. Inhibition of thymic corticosterone production or blockade of the glucocorticoid receptor with RU-486 resulted in enhanced TCR-mediated, antigen-specific deletion of immature thymocytes. These data indicate that locally produced glucocorticoids, because of their antagonism of TCR-mediated signaling for death, may be a key element of antigen-specific thymocyte selection.</description><subject>Aging - physiology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Cholesterol Side-Chain Cleavage Enzyme - biosynthesis</subject><subject>Corticosterone - biosynthesis</subject><subject>Corticosterone - pharmacology</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Desoxycorticosterone - biosynthesis</subject><subject>Epithelial Cells</subject><subject>Epithelium - metabolism</subject><subject>Epithelium - radiation effects</subject><subject>Fetus</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Immunobiology</subject><subject>Lymphocyte Depletion</subject><subject>Lymphoid organs: ontogeny, organization, homing phenomenon</subject><subject>Metyrapone - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mifepristone - pharmacology</subject><subject>Organ Culture Techniques</subject><subject>Pregnenolone - biosynthesis</subject><subject>Receptors, Antigen, T-Cell - drug effects</subject><subject>Receptors, Antigen, T-Cell - physiology</subject><subject>Receptors, Glucocorticoid - drug effects</subject><subject>Receptors, Glucocorticoid - physiology</subject><subject>Signal Transduction</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - metabolism</subject><subject>Thymus Gland - cytology</subject><subject>Thymus Gland - growth & development</subject><subject>Thymus Gland - metabolism</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtLxDAUhYMoOj627oQuxF3rvWmTNC4EEV8guFDXIZNJNdI2Y9IK8-_NOMOgKxchkO_cc084hBwjFAh1df5huwKFLHiBdcm2yARZBblkZb1NJgCU5ggg9sh-jB8AWFWM75LdGiUTiBNy9zzY4N0smwc_G83gfJ-5PhvebTqLbozZRea6eeuMXrKYNT78EG8Wg82ibe3P0CHZaXQb7dH6PiCvtzcv1_f549Pdw_XVY25SrCGf1UKXWGpKQQttBQcjdQNMNg1yKqlhdY2Mcs2ptlJwNp2WQEGCmM6MbVh5QC5XvvNx2tn01g9Bt2oeXKfDQnnt1F_Su3f15r8URZmMMRmcrQ2C_xxtHFTnorFtq3vrx6jSTqxqrP4VIueIVCwjFSuhCT7GYJtNGgS17EiljlTqSHG17CgNnPz-w0a-LiXx0zXX0ei2Cbo3Lm5kFTLkDMpvBLya4w</recordid><startdate>19940601</startdate><enddate>19940601</enddate><creator>VACCHIO, M. 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D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-d87a313a220a7ae760c9af059ff16292c5881526a62ae9765bb3020907bdcef53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Aging - physiology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>Cholesterol Side-Chain Cleavage Enzyme - biosynthesis</topic><topic>Corticosterone - biosynthesis</topic><topic>Corticosterone - pharmacology</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Desoxycorticosterone - biosynthesis</topic><topic>Epithelial Cells</topic><topic>Epithelium - metabolism</topic><topic>Epithelium - radiation effects</topic><topic>Fetus</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Immunobiology</topic><topic>Lymphocyte Depletion</topic><topic>Lymphoid organs: ontogeny, organization, homing phenomenon</topic><topic>Metyrapone - pharmacology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mifepristone - pharmacology</topic><topic>Organ Culture Techniques</topic><topic>Pregnenolone - biosynthesis</topic><topic>Receptors, Antigen, T-Cell - drug effects</topic><topic>Receptors, Antigen, T-Cell - physiology</topic><topic>Receptors, Glucocorticoid - drug effects</topic><topic>Receptors, Glucocorticoid - physiology</topic><topic>Signal Transduction</topic><topic>T-Lymphocytes - cytology</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - metabolism</topic><topic>Thymus Gland - cytology</topic><topic>Thymus Gland - growth & development</topic><topic>Thymus Gland - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VACCHIO, M. 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D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Steroid production in the thymus : implications for thymocyte selection</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>1994-06-01</date><risdate>1994</risdate><volume>179</volume><issue>6</issue><spage>1835</spage><epage>1846</epage><pages>1835-1846</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><coden>JEMEAV</coden><abstract>The mouse thymus was assessed for its ability to produce steroids. Cultured thymic non-T cells produced soluble pregnenolone and deoxycorticosterone, and immunohistochemistry demonstrated steroidogenic enzymes in radioresistant thymic epithelial cells but not in thymocytes. Inhibition of thymic corticosterone production or blockade of the glucocorticoid receptor with RU-486 resulted in enhanced TCR-mediated, antigen-specific deletion of immature thymocytes. These data indicate that locally produced glucocorticoids, because of their antagonism of TCR-mediated signaling for death, may be a key element of antigen-specific thymocyte selection.</abstract><cop>New York, NY</cop><pub>Rockefeller University Press</pub><pmid>8195711</pmid><doi>10.1084/jem.179.6.1835</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of experimental medicine, 1994-06, Vol.179 (6), p.1835-1846 |
| issn | 0022-1007 1540-9538 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Aging - physiology Animals Biological and medical sciences Cells, Cultured Cholesterol Side-Chain Cleavage Enzyme - biosynthesis Corticosterone - biosynthesis Corticosterone - pharmacology Cytochrome P-450 Enzyme System - metabolism Desoxycorticosterone - biosynthesis Epithelial Cells Epithelium - metabolism Epithelium - radiation effects Fetus Fundamental and applied biological sciences. Psychology Fundamental immunology Immunobiology Lymphocyte Depletion Lymphoid organs: ontogeny, organization, homing phenomenon Metyrapone - pharmacology Mice Mice, Inbred BALB C Mifepristone - pharmacology Organ Culture Techniques Pregnenolone - biosynthesis Receptors, Antigen, T-Cell - drug effects Receptors, Antigen, T-Cell - physiology Receptors, Glucocorticoid - drug effects Receptors, Glucocorticoid - physiology Signal Transduction T-Lymphocytes - cytology T-Lymphocytes - drug effects T-Lymphocytes - metabolism Thymus Gland - cytology Thymus Gland - growth & development Thymus Gland - metabolism |
| title | Steroid production in the thymus : implications for thymocyte selection |
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