title: Interleukin-1 beta (IL-1 beta) modulates prostaglandin production and the natural IL-1 receptor antagonist inhibits ovulation in the optimally stimulated rat ovarian perfusion model.
abstract: The rat ovarian perfusion model with bursa removed and intact was used to further characterize the effects of interleukin-1 beta (IL-1 beta) and the natural IL-1 receptor anatagonist (IRAP) on ovulation, steroidogenesis, and prostaglandin production. Twenty-six- to 27-day-old female Sprague-Dawley rats were injected sc with 25 IU PMSG, and 48 h later, the right ovary was dissected (with bursa removed and intact for various experiments) and placed in the perfusion chamber. Ovaries were exposed to various doses of IL-1 beta alone, IL-1 beta with LH, and IL-1 beta with LH and isobutylmethylxanthine (IBMX). The natural IL-1 receptor antagonist was also added to the chambers with LH and IBMX. IL-1 beta at 0.8 (n = 3) and 8.0 (n = 4) nM did not induce LH-independent ovulation in PMSG-stimulated ovaries with bursa removed. In bursa-intact perfusions (n = 3), one ovulation was produced in each compared to control ovaries with bursa intact (n = 3) given an ovulatory trigger of LH alone [2.3 +/- 0.6 (+/- SD) ovulations; P < 0.02]. IL-1 beta enhanced, in a dose- and gonadotropin-dependent fashion, the production of prostaglandin E2 (PGE2) in PMSG-stimulated ovaries with bursa removed given an ovulatory trigger of LH and IBMX compared to that in controls. PGF2 alpha and 6-keto-PGF1 alpha were also modulated by IL-1 beta. Estradiol and progesterone production were not affected. The natural IRAP inhibited ovulation (7.8 +/- 3.9 ovulations vs. 12.4 +/- 1.5; P < 0.04) in PMSG-stimulated ovaries given LH and IBMX as the ovulatory trigger compared to that in controls. This inhibition of ovulation was not associated with reduced steroid or PG levels. IL-1 beta appears to play a potentially significant role in the process of ovulation. The functional importance of the bursa in this model is highlighted in this study. IL-1 beta modulates PG, but not steroid, production. IRAP inhibited ovulation without significantly affecting PG or steroid production.
authors.affiliation: Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City 84132.
authors.forename: C M
authors.initials: CM
authors.lastname: Peterson
authors.forename: H A
authors.initials: HA
authors.lastname: Hales
authors.forename: H H
authors.initials: HH
authors.lastname: Hatasaka
authors.forename: M D
authors.initials: MD
authors.lastname: Mitchell
authors.forename: L
authors.initials: L
authors.lastname: Rittenhouse
authors.forename: K P
authors.initials: KP
authors.lastname: Jones
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis; D004958:Estradiol / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000494:pharmacology; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D010060:Ovulation / Q000187:drug effects*; D010477:Perfusion; D011374:Progesterone / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000494:pharmacology*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011453:Prostaglandins; D012795:Sialoglycoproteins; D011374:Progesterone; D004958:Estradiol; D015121:6-Ketoprostaglandin F1 alpha; D007986:Luteinizing Hormone; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine