Inhibition of Gonadotropin-Induced Testosterone Secretion by the Intracerebroventricular Injection of Interleukin-1β in the Male Rat*

Abstract

Abstract The intracerebroventricular (icv) injection of the proinflammatory cytokine interleukin (IL)-1β 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-1β 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-1β on the hCG-induced T secretory response. Elevations in plasma corticosterone levels do not seem to play a role either, because icv IL-1β 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-1β 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-1β nor IL-6 are important mediators of this effect. Collectively, these results lead us to propose that IL-1β of central origin influences neural pathways linking the brain and the testes, resulting in decreased testicular responses to hCG.