The intracerebroventricular injection of interleukin-1beta blunts the testosterone response to human chorionic gonadotropin: role of prostaglandin- and adrenergic-dependent pathways.

Abstract

The present work extends our previous report that the intracerebroventricular (i.c.v.) injection of interleukin-1beta(IL-1beta, 80 ng) significantly blunted the testosterone response to 1 U/kg human CG (hCG), an effect that we attributed to the stimulation of inhibitory pathways connecting the hypothalamus to the testes. Systemic blockade of prostaglandin-dependent pathways with ibuprofen (alpha-methyl-4-[2-methylpropyl]benzeneacetic acid; sodium salt), which did not, in itself, alter the stimulatory effect of hCG on testosterone release in control rats, modestly, but significantly (P < 0.05) reversed the inhibitory influence of IL-1beta. In contrast, blockade of brain receptors for CRF was unable to alter the effect of IL-1beta, as were lesions of the ventromedial hypothalamic nucleus, a brain area implicated in the control of ovarian function. Blockade of beta-adrenergic receptors significantly prevented the decrease in testicular responsiveness induced by the i.c.v. injection of IL-1beta. Finally, the central injection of the beta-adrenergic agonist isoproterenol, as well as that of norepinephrine, mimicked the ability of icv IL-1beta to blunt testicular secretory activity and produced a marked (P < 0.01) decrease in the response to hCG within 5 min of their administration. We propose that the explanation that best fits our findings is that the i.c.v. injection of IL-1beta activates a neural, catecholamine-dependent pathway that connects the brain and the testes independently of the pituitary.