HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kol, S. Articles by Adashi, E. Y. Search for Related Content PubMed PubMed Citation Articles by Kol, S. Articles by Adashi, E. Y. Agricola Articles by Kol, S. Articles by Adashi, E. Y.

Ovarian Interleukin-1 Receptor Antagonist in Rats: Gene Expression, Cellular Localization, Cyclic Variation, and Hormonal Regulation of a Potential Determinant of Interleukin-1 Action¹

^a Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore, Maryland 21201

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-1ß led to a secondary sIL-1RA peak at 48 h, an effect that was substantially reversed by IL-1RA. This stimulatory effect of IL-1ß 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.

¹ Supported in part by NIH Research Grant HD-30288 (E.Y.A.).

² Correspondence: Eli Y. Adashi, Division of Reproductive Sciences, Departments of Obstetrics and Gynecology, University of Utah Health Science Center, 546 Chipeta Way, Mailbox #20, Salt Lake City, UT 84108. FAX: 801 585 9256; eadashi{at}hsc.utah.edu

³ Current address: Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, Israel.

⁴ Current address: 979 E. 3rd Street, Suite 2000, Chattanooga, TN 37421.

⁵ Current address: Department of Obstetrics and Gynecology, Haemek Medical Center, Afula, Israel.

⁶ Current address: Department of Obstetrics and Gynecology, Tokushima University, Tokushima 770, Japan.

⁷ Current address: Department of Obstetrics and Gynecology, Kyorin University, Tokyo, Japan.

⁸ Current address: Children's Hospital, Boston, MA 02115.

⁹ Current address: Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, UT 84108.

This article has been cited by other articles:

				C. V. Bishop, J. D. Hennebold, and R. L. Stouffer The effects of luteinizing hormone ablation/replacement versus steroid ablation/replacement on gene expression in the primate corpus luteum Mol. Hum. Reprod., March 1, 2009; 15(3): 181 - 193. [Abstract] [Full Text] [PDF]

				A. Martoriati, A.-C. Lalmanach, G. Goudet, and N. Gerard Expression of Interleukin-1 (IL-1) System Genes in Equine Cumulus-Oocyte Complexes and Influence of IL-1{beta} During In Vitro Maturation Biol Reprod, August 1, 2002; 67(2): 630 - 636. [Abstract] [Full Text] [PDF]

				S. Yoshioka, S. Ochsner, D. L. Russell, T. Ujioka, S. Fujii, J. S. Richards, and L. L. Espey Expression of Tumor Necrosis Factor-Stimulated Gene-6 in the Rat Ovary in Response to an Ovulatory Dose of Gonadotropin Endocrinology, November 1, 2000; 141(11): 4114 - 4119. [Abstract] [Full Text] [PDF]