title: The ovarian action of interleukin-1 is receptor mediated: reversal by a naturally occurring interleukin-1 receptor antagonist.
abstract: OBJECTIVE
  To address indirectly the possibility that the ovarian action(s) of interleukin (IL)-1 are receptor mediated and to re-examine the recently reported proposition that the naturally occurring IL-1 receptor antagonist (IL-1ra) may in fact act in the capacity of mixed IL-1 receptor agonist/antagonist.
  
  
  METHODS
  In vitro treatment of isolated granulosa cell (GC) and whole ovarian dispersates of rat origin.
  
  
  RESULTS
  Treatment of GC from immature rats with increasing concentrations of IL-1ra (10 to 5,000 ng/mL) proved without effect on either the basal or FSH (100 ng/mL)-supported accumulation of P. Likewise, cellular viability (as assessed by conversion of 3-[4,5-dimethylthiazol-2-yl]-2-5 diphenyltetrazolium bromide to spectrophotometrically detectable formazan) remained unaltered. However, the concomitant addition of increasing concentrations of IL-1ra (10 to 5,000 ng/mL) yielded dose-dependent reversal of the 10 ng/mL IL-1 beta-mediated inhibition of the FSH-supported accumulation of P. Similarly, the ability of IL-1 beta to exert a dose-dependent (0 to 30 ng/mL) anti-gonadotropic effect was attenuated progressively given the concurrent presence of increasing concentrations (1,000 and 5,000 ng/mL) of IL-1ra. Although treatment of whole ovarian dispersates with 10 ng/mL IL-1 beta resulted in a 5.4-fold increase in the accumulation of prostaglandin (PG)E2, this effect too was all but eliminated after the concomitant addition of 5 micrograms/mL IL-1ra.
  
  
  CONCLUSIONS
  These observations support the nontoxic nature of IL-1ra, confirm its lack of agonistic activity, validate its utility as an experimental probe, and suggest that neither the basal nor the FSH-stimulated accumulation of P are subject to regulation by endogenously produced GC-derived IL-1-like activity. Moreover, these observations suggest that the ability of IL-1 beta to inhibit the gonadotropin-supported accumulation of P and to increase PGE2 accumulation is receptor-mediated.
authors: Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore 21201.
authors: E
authors: E
authors: Kokia
authors: I
authors: I
authors: Ben-Shlomo
authors: E Y
authors: EY
authors: Adashi
mesh_terms: D000818:Animals; D046508:Culture Techniques; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000494:pharmacology
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D015232:Dinoprostone