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.
Turnbull
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AV
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Rivier
C
C
D000315:Adrenalectomy; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
D006063:Chorionic Gonadotropin; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D013739:Testosterone; D007986:Luteinizing Hormone