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This Article Full Text Full Text (PDF) All Versions of this Article: 68/6/2215    most recent biolreprod.102.012211v1 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dixit, V. D. Articles by Sridaran, R. Search for Related Content PubMed PubMed Citation Articles by Dixit, V. D. Articles by Sridaran, R. Agricola Articles by Dixit, V. D. Articles by Sridaran, R.

Gonadotropin-Releasing Hormone Alters the T Helper Cytokine Balance in the Pregnant Rat¹

Department of Physiology,³ Morehouse School of Medicine, Atlanta, Georgia 30310-1495 Division of Parasitic Diseases,⁴ National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30341-3724

The interactions between immune-endocrine and reproductive systems are heightened during pregnancy as an adaptive mechanism, and are regulated by a complex array of hormones and cytokines that control the survival of a semiallogeneic conceptus. GnRH can exert direct effects on the immune system via its receptor (GnRH-R) on lymphoid cells. In the present study, we employed in vitro, ex vivo, and in vivo approaches to investigate the role of GnRH in the modulation of T helper cytokines in pregnant rats undergoing termination of pregnancy. Day 8 pregnant rats were infused with a GnRH agonist (GnRH-Ag) for 24 h using an osmotic minipump. Sham control rats were infused with the vehicle, saline. Lymphocytes were isolated from sham and treated rats and polyclonally stimulated with immobilized anti-CD3 antibody. The levels of the signature T helper 1 (Th-1) cytokines (interferon- [IFN-] and interleukin-2 [IL-2]) and Th-2 cytokines (IL-4 and IL-10) were measured in culture supernatants. Using immunoflourescence confocal microscopy, we demonstrated for the first time the spatial localization of GnRH-R protein on the surface of lymphocytes. We observed a marked increase in IFN- and inhibition of IL-4 production from lymphocytes of pregnant rats treated in vitro with different doses of GnRH-Ag. Further, the responsiveness of lymphocytes to produce IFN- was markedly increased in cells cultured ex vivo from GnRH-Ag infused rats, whereas the capacity of lymphocytes to produce IL-4 was significantly inhibited. In addition, GnRH-Ag infusion in pregnant rats induced a shift toward Th-1 cytokines in the serum. We did not observe any significant difference in IL-2 and IL-10 production in response to GnRH-Ag. Our results suggest an additional function for GnRH as a Th-1 inducer and Th-2 inhibitor. GnRH can thus skew the cytokine balance to predominantly Th-1 type in pregnancy, leading to the termination of pregnancy in rats.

¹ This study was supported by grants GM08248 and HD41749 from the National Institutes of Health (NIH) and grant NAG9-963 from the National Aeronautics and Space Administration (NASA) to R.S. Core facilities were supported by grants NCC9-53 from NASA and RR03034 from NIH.

² Correspondence: Rajagopala Sridaran, Department of Physiology, Morehouse School of Medicine, 720 Westview Drive, S.W., Atlanta, GA 30310-1495. FAX: 404 752 1045; sridaran{at}msm.edu