{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:06:20Z","timestamp":1791025580754,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,1,2]],"date-time":"2013-01-02T00:00:00Z","timestamp":1357084800000},"content-version":"vor","delay-in-days":2798,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Andrology"],"published-print":{"date-parts":[[2005,5,6]]},"abstract":"<jats:p><jats:bold>ABSTRACT: <\/jats:bold> Leydig cells have been implicated in several inflammation\u2010related responses of the testis. Specifically, these cells produce the proinflammatory cytokines interleukin\u20101 (IL\u20101) and IL\u20106, stimulate macrophage recruitment, and promote interstitial fluid formation. In addition, the immunoregulatory cytokines macrophage migration inhibitory factor (MIF), transforming growth factor\u2010\u03b21 (TGF\u03b21), and interferon\u2010\u03b3 (IFN\u03b3) are constitutively expressed by testicular cells, including the Leydig cells. In the present study, the contribution of the Leydig cell to testicular inflammatory responses was examined in adult male rats treated with the Leydig cell\u2014specific toxin, ethane dimethane sulfonate (EDS). Intratesticular testosterone levels were modulated by subcutaneous testosterone implants. After 10 days, animals received an injection of lipopolysaccharide (LPS) to induce an inflammatory response, or saline alone, and were killed 3 hours later. Both depletion of Leydig cells by EDS and LPS treatment caused a decrease in collected testicular interstitial fluid to about 35% of control levels, but the effects were not additive. Maintenance of intratesticular testosterone reversed the interstitial fluid decline following EDS treatment and partially prevented the LPS\u2010induced effect. MIF, TGF\u03b21, and IFN\u03b3 were expressed in both the normal and inflamed testis at similar levels. In contrast, EDS treatment caused a significant decline in expression of all 3 cytokines, which was prevented by the testosterone implants. These data indicate that 1) expression of TGF\u03b21, MIF, and IFN\u03b3 in the testis is not dependent on the presence of intact Leydig cells but is under direct testosterone control and 2) the decline in testicular interstitial fluid during inflammation involves the Leydig cells, acting via both androgens and nonandrogenic secretions. These data provide further support for a significant role for the Leydig cell in modulating the testicular response to inflammation.<\/jats:p>","DOI":"10.2164\/jandrol.04149","type":"journal-article","created":{"date-parts":[[2005,5,2]],"date-time":"2005-05-02T19:28:15Z","timestamp":1115062095000},"page":"379-386","source":"Crossref","is-referenced-by-count":22,"title":["Regulatory Cytokine Expression and Interstitial Fluid Formation in the Normal and Inflamed Rat Testis Are Under Leydig Cell Control"],"prefix":"10.1002","volume":"26","author":[{"given":"Mark","family":"Hedger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Klug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suada","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Meinhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.134.5.8156908"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0890023"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.10.8828518"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod56.2.357"},{"key":"e_1_2_6_6_1","first-page":"532","article-title":"A reagent for the single\u2010step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples","volume":"15","author":"Chomczynski P.","year":"1993","journal-title":"Biotechniques"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1996.tb00466.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0970115"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1992.tb01353.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.133.1.8319585"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.11.4925"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-002-0547-6"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/8.6.518"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.125.1.87"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1680193"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-1-3"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.141.11.4000"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1353\/pbm.1985.0038"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(02)00016-5"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1994.tb00502.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(02)00060-8"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod58.4.935"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10412"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod53.6.1407"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00225571"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.141.10.3679"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1200215"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.11.8895383"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod59.2.371"},{"issue":"9","key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1242\/jcs.112.9.1337","article-title":"A switch in the cellular localization of macrophage migration inhibitory factor in the rat testis after ethane dimethane sulfonate treatment","volume":"112","author":"Meinhardt A.","year":"1999","journal-title":"J Cell Sci"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.7.1.67"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod63.5.1285"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.1.7240"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.9.4480"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD9900291"},{"key":"e_1_2_6_36_1","first-page":"1063","volume-title":"The Physiology of Reproduction","author":"Setchell BP","year":"1994"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.0910245"},{"key":"e_1_2_6_38_1","first-page":"352","article-title":"Down\u2010regulation of the expression of three major rat liver cytochrome P450S by endotoxin in vivo occurs independently of nitric oxide production","volume":"287","author":"Sewer MB","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1280359"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0690125"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001880103"},{"key":"e_1_2_6_42_1","first-page":"52","article-title":"The interleukin\u20101 system in the testis","volume":"32","author":"Soder O.","year":"2000","journal-title":"Andrologia"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(97)00172-X"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0870795"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.132.1.8380379"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod48.1.40"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(86)90138-3"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod51.3.551"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.132.6.2438"}],"container-title":["Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.2164%2Fjandrol.04149","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.2164\/jandrol.04149","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T04:16:25Z","timestamp":1697516185000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.2164\/jandrol.04149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5,6]]},"references-count":48,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,5,6]]}},"alternative-id":["10.2164\/jandrol.04149"],"URL":"https:\/\/doi.org\/10.2164\/jandrol.04149","archive":["Portico"],"relation":{},"ISSN":["0196-3635","1939-4640"],"issn-type":[{"value":"0196-3635","type":"print"},{"value":"1939-4640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5,6]]}}}