title: Regulatory cytokine expression and interstitial fluid formation in the normal and inflamed rat testis are under leydig cell control.
abstract: Leydig cells have been implicated in several inflammation-related responses of the testis. Specifically, these cells produce the proinflammatory cytokines interleukin-1 (IL-1) and IL-6, stimulate macrophage recruitment, and promote interstitial fluid formation. In addition, the immunoregulatory cytokines macrophage migration inhibitory factor (MIF), transforming growth factor-beta1 (TGFbeta1), and interferon-gamma (IFNgamma) 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-specific 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-induced effect. MIF, TGFbeta1, and IFNgamma 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 TGFbeta1, MIF, and IFNgamma 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.
authors.affiliation: Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Hedger
authors.forename: Jörg
authors.initials: J
authors.lastname: Klug
authors.forename: Suada
authors.initials: S
authors.lastname: Fröhlich
authors.forename: Ruth
authors.initials: R
authors.lastname: Müller
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinhardt
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D045604:Extracellular Fluid / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D007985:Leydig Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis; D008297:Male; D008698:Mesylates / Q000494:pharmacology; D009920:Orchitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D008698:Mesylates; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013739:Testosterone; D007371:Interferon-gamma; C002994:ethylene dimethanesulfonate