Inhibition of gonadotropin-induced testosterone secretion by the intracerebroventricular injection of interleukin-1 beta in the male rat.

The intracerebroventricular (icv) injection of the proinflammatory cytokine interleukin (IL)-1 beta is known to significantly decrease plasma LH levels in the male rat, thereby lowering testosterone (T) secretion. We show here that central administration of this cytokine (20-80 ng) also inhibits T secretion in response to human CG (hCG), an effect that is apparent already when IL-1 beta is injected 15 min before hCG. This phenomenon is independent of LH secretion because lowering LH levels with the potent GnRH antagonist Azaline B neither mimics nor affects the suppressive influence of icv IL-1 beta on the hCG-induced T secretory response. Elevations in plasma corticosterone levels do not seem to play a role either, because icv IL-1 beta is able to blunt hCG-induced T secretion in animals whose corticosterone has been removed by adrenalectomy or reduced by the administration of antibodies to CRF. Furthermore, the observation that icv IL-1 beta inhibits the T response to hCG before elevations in plasma IL-6 concentrations are detectable, and that central treatment with the cytokine is more effective than iv treatment, indicates that circulating levels of neither IL-1 beta nor IL-6 are important mediators of this effect. Collectively, these results lead us to propose that IL-1 beta of central origin influences neural pathways linking the brain and the testes, resulting in decreased testicular responses to hCG.