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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 4 1765
Copyright © 2001 by The Endocrine Society


Original Studies

Regulated Expression of Prostaglandin E2 Receptors EP2 and EP4 in Human Ovarian Granulosa-Luteal Cells

Kirsi Narko, Kirsi Saukkonen, Ilkka Ketola, Ralf Bützow, Markku Heikinheimo and Ari Ristimäki

Department of Obstetrics and Gynecology (K.N., K.S., R.B., A.R.), Department of Pathology (R.B., A.R.), and Children’s Hospital (I.K., M.H.), Helsinki University Central Hospital and Haartman Institute, University of Helsinki, Finland; Department of Pediatrics (M.H.), Washington University, St. Louis, Missouri

Prostaglandins (PGs) have been implicated in regulation of ovarian function. We have previously shown that the expression of cyclooxygenase-2 and the receptor for PGF2{alpha} are expressed in periovulatory human granulosa cells and upregulated by gonadotropins and cytokines in cultured human ovarian granulosa-luteal (GL) cells. We now show that transcripts for PGE2 receptor subtypes EP2 and EP4 are expressed in freshly isolated human granulosa cells and in mouse ovaries as detected by Northern blot analysis. However, EP2 and EP4 receptor mRNA levels were low or nondetectable in cultured human GL cells suggesting that these transcripts may be under hormonal and/or cytokine regulation in the ovaries in vivo. Indeed, the proinflammatory cytokine interleukin-1ß (IL-1ß) stimulated expression of EP2 and EP4 transcripts in concentration- and time-dependent manner in the GL cells. Furthermore, the transcript for EP2 receptor was localized in the corpus luteum of the mouse ovary by in situ hybridization, and EP2 protein was expressed in human corpus luteum as detected by immunohistochemistry. Our data suggest that IL-1ß induces expression of EP2 and EP4 receptors in human GL cells, and that EP2 receptor is expressed in both human and murine luteal glands.




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