The inhibitory effect of intracerebroventricularly injected interleukin 1 beta on testosterone secretion in the rat: Role of steroidogenic acute regulatory protein

Exposure to disease or injury often results in impaired reproductive activi ty accompanied by decreased testosterone levels. After immune activation, t he cytokine interleukin 1-beta (IL-1 beta) circulates in high concentration s, and its exogenous administration evokes many of the sequelae of immune a ctivation. Previously, we have shown that the administration of this cytoki ne into the cerebral ventricles blunts hCG-stimulated testosterone secretio n. This effect, though time-dependent, occurs before significant elevation of interleukin 6 in the peripheral bloodstream, does not depend on adrenal activation, and/or changes in LH concentrations, leading us to hypothesize a direct connection between the brain and testis, To explore this mechanism further, we isolated testicular tissue from rats treated intracerebroventr icularly (icv) with vehicle or IL-1 beta 30 or 90 min before they were kill ed. We found that in vivo cytokine treatment blunted ex vivo testosterone s ecretion in response to hCG, showing that the mechanism is independent of c irculating cytokines. Though hCG binding was moderately reduced by icy IL-1 beta in these preparations, the extent of this inhibition did not explain our observations. As the first acutely and hormonally regulated step in the biosynthesis of testosterone is the transfer of cholesterol into the inner mitochondrial membrane, which is mediated by steroidogenic acute regulator y (StAR) protein, we hypothesized that the rapid effects of icy IL-1 beta o n testicular responsiveness to hCG might be due to reduced levels of StAR. We report here that StAR protein was indeed reduced in Leydig cells isolate d from rats treated in vivo with IL-1 beta, Furthermore, treatment with a w ater-permeable form of cholesterol that bypasses the requirement for StAR p artially restored hCG-stimulated testosterone secretion from testes isolate d from rats treated icy with IL-1 beta, Taken together, our data indicate t hat StAR plays a role in the suppression of testicular function evoked by c entral administration of IL-1 beta.