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 Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Telleria, C. M. Articles by Gibori, G. Search for Related Content PubMed PubMed Citation Articles by Telleria, C. M. Articles by Gibori, G.

The Expression of Interleukin-6 in the Pregnant Rat Corpus Luteum and Its Regulation by Progesterone and Glucocorticoid¹

Department of Physiology and Biophysics, College of Medicine, University of Illinois, Chicago, Illinois 60612

Address all correspondence and requests for reprints to: Dr. Geula Gibori, Department of Physiology and Biophysics (M/C 901), University of Illinois, 835 South Wolcott Avenue, Chicago, Illinois 60612-7342. E-mail: ggibori{at}uic.edu

Interleukin (IL)-6, a multifunctional cytokine originally described as a T cell-derived factor, is also produced by different cell types, and it influences a wide variety of physiological and pathophysiological processes. Recent studies further suggest that IL-6 has a role in down-regulating hormone production by endocrine organs and can negatively affect the steroidogenic capacity of both ovaries and testes. Thus, the aims of this investigation were to examine whether IL-6 plays a role in luteolysis and, more specifically, to determine whether luteal cells express the IL-6 gene, whether this expression is developmentally and hormonally regulated in pregnancy, and whether the corpus luteum could be a target for IL-6 action. Using semiquantitative RT-PCR, messenger RNA (mRNA) encoding both components of the IL-6 receptor [the ligand-binding subunit (IL-6 R) and the IL-6 R-associated signal transducer (gp130)] were found to be highly expressed in corpora lutea throughout pregnancy. In contrast, IL-6 mRNA expression was barely detectable from day 4 through the end of pregnancy, whereas a sharp and abrupt expression of IL-6 mRNA occurred immediately after parturition. Although the corpus luteum does not express IL-6 mRNA during most of pregnancy, it could be induced to express this gene with an in vivo injection of the bacterial endotoxin, lipopolysaccharide. In addition, when corpora lutea from day-15 pregnant rats were isolated and maintained in culture, IL-6 mRNA that was undetectable at 0 h increased in a time-related manner and reached significant levels after 4 h of incubation, followed by a similar increase in IL-6 protein secreted in the culture media. Isolation of the small and large luteal cells by elutriation indicated that both cell populations can secrete IL-6 in culture. The apparent ability of luteal cells to spontaneously express IL-6 in vitro, together with the lack of IL-6 expression during most of pregnancy, led us to examine whether the IL-6 gene is silenced throughout pregnancy by luteotropic hormones. Corpora lutea from day-15 pregnant rats were cultured in the presence of different doses of progesterone; the synthetic glucocorticoid, dexamethasone; 17ß-estradiol; and PRL. Progesterone and dexamethasone markedly inhibited IL-6 mRNA expression, whereas 17ß-estradiol had a minimal inhibitory effect, and PRL did not affect IL-6 mRNA expression. In summary, results of this investigation have revealed that the rat corpus luteum expresses the IL-6 receptor system and that luteal cells are able to secrete IL-6. However, IL-6 gene expression is silenced during most of pregnancy, probably by the high levels of progesterone locally produced in the corpus luteum. The salient finding that progesterone and glucocorticoid strongly inhibit the expression of IL-6 in the corpus luteum suggests that one important luteotropic role of progesterone and glucocorticoids could be to prevent the expression of IL-6, which might have a deleterious effect on luteal function.

This article has been cited by other articles:

				M. J Cannon, J. S Davis, and J. L Pate The class II major histocompatibility complex molecule BoLA-DR is expressed by endothelial cells of the bovine corpus luteum Reproduction, May 1, 2007; 133(5): 991 - 1003. [Abstract] [Full Text] [PDF]

				C. Stocco, C. Telleria, and G. Gibori The Molecular Control of Corpus Luteum Formation, Function, and Regression Endocr. Rev., February 1, 2007; 28(1): 117 - 149. [Abstract] [Full Text] [PDF]

				A H K El-Hashash and S J Kimber Trophoblast differentiation in vitro: establishment and characterisation of a serum-free culture model for murine secondary trophoblast giant cells Reproduction, July 1, 2004; 128(1): 53 - 71. [Abstract] [Full Text] [PDF]

				A. A. Goyeneche, R. P. Deis, G. Gibori, and C. M. Telleria Progesterone Promotes Survival of the Rat Corpus Luteum in the Absence of Cognate Receptors Biol Reprod, January 1, 2003; 68(1): 151 - 158. [Abstract] [Full Text] [PDF]

				W. N. Jefferson, J. F. Couse, E. Padilla-Banks, K. S. Korach, and R. R. Newbold Neonatal Exposure to Genistein Induces Estrogen Receptor (ER){alpha} Expression and Multioocyte Follicles in the Maturing Mouse Ovary: Evidence for ER{beta}-Mediated and Nonestrogenic Actions Biol Reprod, October 1, 2002; 67(4): 1285 - 1296. [Abstract] [Full Text] [PDF]

				F. Gaytan, C. Morales, C. Bellido, and J. E. Sanchez-Criado Selective Apoptosis of Luteal Endothelial Cells in Dexamethasone-Treated Rats Leads to Ischemic Necrosis of Luteal Tissue Biol Reprod, January 1, 2002; 66(1): 232 - 240. [Abstract] [Full Text]

				S. Deb, C. Tessier, A. Prigent-Tessier, U. Barkai, S. Ferguson-Gottschall, R. K. Srivastava, J. Faliszek, and G. Gibori The Expression of Interleukin-6 (IL-6), IL-6 Receptor, and gp130-Kilodalton Glycoprotein in the Rat Decidua and a Decidual Cell Line: Regulation by 17{beta}-Estradiol and Prolactin Endocrinology, October 1, 1999; 140(10): 4442 - 4450. [Abstract] [Full Text]

				R. Towns, K.M.J. Menon, R. K. Brabec, A. M. Silverstein, J. M. Cohen, J. M. Bowen, and P. L. Keyes Glucocorticoids Stimulate the Accumulation of Lipids in the Rat Corpus Luteum Biol Reprod, August 1, 1999; 61(2): 416 - 421. [Abstract] [Full Text]

				O. Ogueh, J. Jones, H. Mitchell, J. Alaghband-Zadeh, and M.R. Johnson Effect of antenatal dexamethasone therapy on maternal plasma human chorionic gonadotrophin, oestradiol and progesterone Hum. Reprod., February 1, 1999; 14(2): 303 - 306. [Abstract] [Full Text] [PDF]