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The Intracerebroventricular Injection of Interleukin-1ß Blunts the Testosterone Response to Human Chorionic Gonadotropin: Role of Prostaglandin- and Adrenergic-Dependent Pathways¹

Ligand Pharmaceuticals (K.O.), Department of Pharmacology, San Diego, California 92121; and The Clayton Foundation Laboratories for Peptide Biology (C.R.), The Salk Institute, La Jolla, California 92037

Address all correspondence and requests for reprints to: Catherine Rivier, The Clayton Foundation Laboratories for Peptide Science, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037. E-mail: crivier{at}salk.edu

The present work extends our previous report that the intracerebroventricular (icv) injection of interleukin-1ß (IL-1ß, 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 (-methyl-4-[2-methyl-propyl]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-1ß. In contrast, blockade of brain receptors for CRF was unable to alter the effect of IL-1ß, as were lesions of the ventromedial hypothalamic nucleus, a brain area implicated in the control of ovarian function. Blockade of ß-adrenergic receptors significantly prevented the decrease in testicular responsiveness induced by the icv injection of IL-1ß. Finally, the central injection of the ß-adrenergic agonist isoproterenol, as well as that of norepinephrine, mimicked the ability of icv IL-1ß 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 icv injection of IL-1ß activates a neural, catecholamine-dependent pathway that connects the brain and the testes independently of the pituitary.

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