The intracerebroventricular injection of interleukin-1beta blunts the testosterone response to human chorionic gonadotropin: role of prostaglandin- and adrenergic-dependent pathways.
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.
Ogilvie
K
K
Ligand Pharmaceuticals, Department of Pharmacology, San Diego, California 92121, USA.
Rivier
C
C
D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000502:physiology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D054832:Urocortins; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D006063:Chorionic Gonadotropin; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D011453:Prostaglandins; D011941:Receptors, Adrenergic; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D013739:Testosterone; D003346:Corticotropin-Releasing Hormone