Endocrinology, Vol 133, 2431-2436, Copyright © 1993 by Endocrine Society

ARTICLES

The chronic intracerebroventricular infusion of interleukin-1 beta alters the activity of the hypothalamic-pituitary-gonadal axis of cycling rats. II. Induction of pseudopregnant-like corpora lutea

C Rivier and G Erickson
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.

The acute administration of interleukin-1 beta (IL-1 beta) into the brain ventricles of rats has been shown to cause a significant decrease in plasma LH levels, a phenomenon primarily mediated through inhibition of LHRH release. However, there are no studies of the long-term consequences of IL-1 beta injected intracerebroventricularly on the hypothalamic-pituitary-gonadal axis. In particular, we became interested in determining whether IL-1 beta exerts deleterious effects on reproductive parameters, and to what extent they might be caused by a lowering of circulating gonadotropins. In the present experiments, we therefore investigated the effects of the infusion of IL-1 beta to intact cycling female rats and compared them to those observed in rats injected with a potent LHRH antagonist. Although blockade of LHRH receptors caused a modest and delayed inhibition of progesterone secretion, infusion of IL-1 beta (4 ng/h for 4-6 days) was accompanied by persistent and significant increases in plasma P4 levels. In these rats, the PRL release was erratic, with low values during the morning and generally extremely elevated values during the night. The volume of the corpora lutea-I (CL-I) of rats exposed to IL-1 beta, but not to the vehicle or the LHRH antagonist, was significantly increased, and the lutein cells showed extensive hypertrophy. These results indicate that prolonged infusion of IL-1 beta into the brain of cycling rats blocks luteolysis in newly formed CL. These changes were not present in rats injected with the LHRH antagonist, suggesting that they were not primarily related to decreases in gonadotropin secretion. We propose that the high plasma PRL levels may play a role in the changes in ovarian activity which we observed, through other mechanisms, such as sustained increases in adrenal epinephrine and/or glucocorticoids, may also be involved. These findings indicate a novel role for central IL-1 beta in the prevention of luteolysis and the transformation of the CL of the cycle into a CL of pseudopregnancy.

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