In the Rat, Interleukin- 1α Acts at the Level of the Brain and the Gonads to Interfere with Gonadotropin and Sex Steroid Secretion*

Abstract

These studies were designed to investigate a possible effect of the monokine interleukin-1 alpha (Il-1 alpha) on gonadotropins and/or sex steroid secretion. Three putative sites of action were considered: the central nervous system, the pituitary, and the gonads. A central nervous system-mediated mechanism was tested by injecting Il-1 alpha into the lateral ventricle of the brain of castrated rats; this treatment caused a dose-related inhibition of LH secretion, with a minimum effective dose below 0.1 microgram (6.6 pmol) and a maximum effect at 1 microgram (66 pmol). The plateau response was observed 120 min after injection. The possibility that Il-1 alpha might alter pituitary sensitivity was studied by administering 200 ng GnRH, iv, into gonadectomized control rats or rats pretreated with 1 micrograms Il-1 alpha intracerebroventricularly. GnRH induced a comparable increase in the plasma LH levels of both groups of animals. Finally, hypophysectomized immature (24-day-old) female rats were used to determine if we could confirm in vivo that interleukin-1 alpha can act directly at the level of the ovary to interfere with steroidogenesis. In these animals, the sc injection of 20 IU PMSG produced a marked (P less than 0.01) increase in plasma estradiol levels, while the sequential injection of 20 IU PMSG and 1 microgram hCG significantly (P less than 0.01) stimulated progesterone release. The ip administration of 1 microgram Il-1 alpha every 12 h to gonadotropin-treated rats resulted in a significant inhibition of both estradiol and progesterone secretion. The results support possible roles for Il-1 alpha at the levels of the brain and the gonads, but not the pituitary, to inhibit reproductive functions.