THE CHRONIC INTRACEREBROVENTRICULAR INFUSION OF INTERLEUKIN-1-BETA ALTERS THE ACTIVITY OF THE HYPOTHALAMIC-PITUITARY-GONADAL AXIS OF CYCLING RATS .2. INDUCTION OF PSEUDOPREGNANT-LIKE CORPORA-LUTEA

The acute administration of interleukin-1beta (IL-1beta) into the brai n 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 conseq uences of IL-1beta injected intracerebroventricularly on the hypothala mic-pituitary-gonadal axis. In particular, we became interested in det ermining whether IL-1beta exerts deleterious effects on reproductive p arameters, and to what extent they might be caused by a lowering of ci rculating gonadotropins. In the present experiments, we therefore inve stigated the effects of the infusion of IL-1beta to intact cycling fem ale rats and compared them to those observed in rats injected with a p otent LHRH antagonist. Although blockade of LHRH receptors caused a mo dest and delayed inhibition of progesterone secretion, infusion of IL- 1beta (4 ng/h for 4-6 days) was accompanied by persistent and signific ant increases in plasma P4 levels. In these rats, the pattern of PRL r elease was erratic, with low values during the morning and generally e xtremely elevated values during the night. The volume of the corpora l utea-I (CL-I) of rats exposed to IL-1beta, but not to the vehicle or t he LHRH antagonist, was significantly increased, and the lutein cells showed extensive hypertrophy. These results indicate that prolonged in fusion of IL-1beta 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 plasm a 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. Thes e findings indicate a novel role for central IL-1beta in the. preventi on of luteolysis and the transformation of the CL of the cycle into a CL of pseudopregnancy.