Differential effects of dexamethasone treatment on lipopolysaccharide-induced testicular inflammation and reproductive hormone inhibition in adult rats

A single intraperitoneal injection of Lipopolysaccharide (LPS) causes a bip hasic suppression of testicular steroidogenesis in adult rats, with inhibit ion at 6 h and 18-24 h after injection. The inhibition of steroidogenesis i s independent of the reduction in circulating LH that also occurs after LPS treatment, indicating a direct effect of inflammation at the Leydig cell l evel. The relative contributions to this inhibition by intratesticular vers us systemic responses to inflammation, including the adrenal glucocorticoid s, was investigated in this study. Adult male Wistar rats (eight/group) received injections of LPS (0.1 mg/kg i.p.), dexamethasone (DEX; 50 mug/kg i.p.), LPS and DEX, or saline only (co ntrols), and were killed 6 h, 18 h and 72 h later. Treatment with LPS stimu lated body temperature and serum corticosterone levels measured 6 h later. Administration of DEX had no effect on body temperature, but suppressed ser um 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 fo r interleukin-1 beta (IL-1 beta), the principal inflammatory cytokine, was increased in both testis and liver of LPS-treated rats. Serum LH and testos terone 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 inh ibited basal IL-1 beta expression and the LPS-induced increase of IL-1 beta mRNA levels in the liver, but had no effect on IL-1 beta in the testis. Th e effects of DEX on IL-1 beta levels in the liver were no longer evident by 18 h. In LPS-treated rats, DEX caused a significant reversal of the inhibi tion of serum LH and testosterone at 18 h, although not at 6 h or 72 h. Acc ordingly, DEX inhibited the systemic inflammatory response, but had no dire ct effect on either testicular steroidogenesis or intra-testicular inflamma tion, 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 co ntrast, the later Leydig cell inhibition (at 18 h) may be attributable to e xtra-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 Le ydig cell inhibition following LPS administration are due to separate mecha nisms.