title: Differential effects of dexamethasone treatment on lipopolysaccharide-induced testicular inflammation and reproductive hormone inhibition in adult rats.
abstract: A single intraperitoneal injection of lipopolysaccharide (LPS) causes a biphasic suppression of testicular steroidogenesis in adult rats, with inhibition at 6 h and 18-24 h after injection. The inhibition of steroidogenesis is independent of the reduction in circulating LH that also occurs after LPS treatment, indicating a direct effect of inflammation at the Leydig cell level. The relative contributions to this inhibition by intratesticular versus systemic responses to inflammation, including the adrenal glucocorticoids, was investigated in this study. Adult male Wistar rats (eight/group) received injections of LPS (0.1 mg/kg i.p.), dexamethasone (DEX; 50 microg/kg i.p.), LPS and DEX, or saline only (controls), and were killed 6 h, 18 h and 72 h later. Treatment with LPS stimulated body temperature and serum corticosterone levels measured 6 h later. Administration of DEX had no effect on body temperature, but suppressed serum corticosterone levels. At the dose used in this study, DEX alone had no effect on serum LH or testosterone at any time-point. Expression of mRNA for interleukin-1beta (IL-1beta), the principal inflammatory cytokine, was increased in both testis and liver of LPS-treated rats. Serum LH and testosterone levels were considerably reduced at 6 h and 18 h after LPS treatment, and had not completely recovered by 72 h. At 6 h after injection, DEX inhibited basal IL-1beta expression and the LPS-induced increase of IL-1beta mRNA levels in the liver, but had no effect on IL-1beta in the testis. The effects of DEX on IL-1beta levels in the liver were no longer evident by 18 h. In LPS-treated rats, DEX caused a significant reversal of the inhibition of serum LH and testosterone at 18 h, although not at 6 h or 72 h. Accordingly, DEX inhibited the systemic inflammatory response, but had no direct effect on either testicular steroidogenesis or intra-testicular inflammation, at the dose employed. These data suggest that the inhibition of Leydig cell steroidogenesis at 6 h after LPS injection, which was not prevented by co-administration of DEX, is most likely due to direct actions of LPS at the testicular level. In contrast, the later Leydig cell inhibition (at 18 h) may be attributable to extra-testicular effects of LPS, such as increased circulating inflammatory mediators or the release of endogenous glucocorticoids, that were inhibited by DEX treatment. These data indicate that the early and late phases of Leydig cell inhibition following LPS administration are due to separate mechanisms.
authors.affiliation: Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria 3168, Australia.
authors.forename: R M
authors.initials: RM
authors.lastname: Gow
authors.forename: M K
authors.initials: MK
authors.lastname: O'Bryan
authors.forename: B J
authors.initials: BJ
authors.lastname: Canny
authors.forename: G T
authors.initials: GT
authors.lastname: Ooi
authors.forename: M P
authors.initials: MP
authors.lastname: Hedger
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000235:genetics; D007985:Leydig Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides; D008099:Liver / Q000276:immunology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009920:Orchitis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013739:Testosterone; D003907:Dexamethasone; D007986:Luteinizing Hormone; D003345:Corticosterone