title: In the rat, interleukin-1 alpha 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.
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
authors.forename: C
authors.initials: C
authors.lastname: Rivier
authors.forename: W
authors.initials: W
authors.lastname: Vale
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D004347:Drug Interactions; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006062:Gonadotropins / Q000378:metabolism*; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006066:Gonads / Q000502:physiology*; D007016:Hypophysectomy; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009919:Orchiectomy; D010060:Ovulation / Q000187:drug effects; D010906:Pituitary Hormone-Releasing Hormones / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D006064:Gonadotropins, Equine; D007375:Interleukin-1; D010906:Pituitary Hormone-Releasing Hormones