Ovarian interleukin-1 receptor antagonist in rats: Gene expression, cellular localization, cyclic variation, and hormonal regulation of a potential determinant of interleukin-1 action

Shahar Kol, Barry W. Donesky, Kristiina R Altman, Izhar Ben-Shlomo, Minora Lrahara, Motomu Ando, Richard M. Rohan, Eli Y. Adashi

Research output: Contribution to journalArticle

Abstract

It is hypothesized that the intraovarian interleukin (IL)-1 system plays a prominent role in the regulation of follicular development and ovulation. A central component of the intraovarian IL-1 system is the IL-1 receptor antagonist (IL-1RA), a protein acting as a pure IL-1 receptor antagonist and one for which intracellular (icIL-1RA) and secretory (sIL-1RA) varieties have been described. It was the objective of this study to explore rat ovarian IL- 1RA gene expression, to establish the identity and relative abundance of its alternative transcripts, to study its cellular localization, to determine its cyclic variation, and to assess its hormonal regulation. Protected IL-1RA cDNA fragments corresponding to either sIL-1RA or icIL-1RA were barely detectable in untreated whole ovarian tissue of immature rat origin. However, sIL-1RA transcripts reached a maximal value (3.3-fold increase over untreated control values; p <0.05) 12 h after hCG administration (time of projected ovulation). In situ hybridization localized IL-1RA to mural, antral, and cumulus granulosa cells. Modestly intense staining was also apparent in oocytes. The basal pattern of sIL-1RA expression by cultured whole ovarian dispersates was characterized by a spontaneous increase to a peak value at 4 h. The early (4 h) sIL-1RA burst proved IL-1-, nitric oxide-, and protein biosynthesis-independent. However, treatment with IL-1β led to a secondary sIL-1RA peak at 48 h, an effect that was substantially reversed by IL-1RA. This stimulatory effect of IL-1β on IL-1RA expression proved relatively specific, and nitric oxide independent, but contingent upon de novo protein biosynthesis. The in vitro expression of icIL-1RA was barely detectable. Taken together, these in vivo and in vitro observations 1) document the rat ovary as a site of IL-1RA (sIL-1RA > cIL-1RA) expression, 2) localize the relevant transcripts to the granulosa cell, 3) disclose peak expression at the time of ovulation, and 4) establish IL-1 dependence.

Original languageEnglish (US)
Pages (from-to)274-282
Number of pages9
JournalBiology of Reproduction
Volume61
Issue number1
DOIs
StatePublished - 1999

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Interleukin-1 Receptors
Interleukin-1
Interleukins
Ovulation
Gene Expression
Interleukin 1 Receptor Antagonist Protein
Granulosa Cells
Complementary DNA

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

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Ovarian interleukin-1 receptor antagonist in rats : Gene expression, cellular localization, cyclic variation, and hormonal regulation of a potential determinant of interleukin-1 action. / Kol, Shahar; Donesky, Barry W.; Altman, Kristiina R; Ben-Shlomo, Izhar; Lrahara, Minora; Ando, Motomu; Rohan, Richard M.; Adashi, Eli Y.

In: Biology of Reproduction, Vol. 61, No. 1, 1999, p. 274-282.

Research output: Contribution to journalArticle

Kol, Shahar ; Donesky, Barry W. ; Altman, Kristiina R ; Ben-Shlomo, Izhar ; Lrahara, Minora ; Ando, Motomu ; Rohan, Richard M. ; Adashi, Eli Y. / Ovarian interleukin-1 receptor antagonist in rats : Gene expression, cellular localization, cyclic variation, and hormonal regulation of a potential determinant of interleukin-1 action. In: Biology of Reproduction. 1999 ; Vol. 61, No. 1. pp. 274-282.
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AU - Altman, Kristiina R

AU - Ben-Shlomo, Izhar

AU - Lrahara, Minora

AU - Ando, Motomu

AU - Rohan, Richard M.

AU - Adashi, Eli Y.

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