This Article Full Text Full Text (PDF) All Versions of this Article: 149/6/2782    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart 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 Google Scholar Articles by Zhao, P. Articles by Hsueh, A. J. W. PubMed PubMed Citation Articles by Zhao, P. Articles by Hsueh, A. J. W.

Gonadotropin Stimulation of Ovarian Fractalkine Expression and Fractalkine Augmentation of Progesterone Biosynthesis by Luteinizing Granulosa Cells

State Key Laboratory of Reproductive Biology (P.Z., Z.H., E.-K.D.), Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China; Graduate School of the Chinese Academy of Sciences (P.Z., Z.H.), Beijing 100039, People’s Republic of China; Department of Obstetrics and Gynecology (A.D., J.L., A.J.W.H.), Division of Reproductive Biology, Stanford University School of Medicine, Stanford, California 94305-5317; and Organon (S.M.M., M.D.S.G.), 5349 AB, Oss, The Netherlands

Address all correspondence and requests for reprints to: En-Kui Duan, Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China. E-mail: duane{at}ioz.ac.cn; or Aaron J. W. Hsueh, Department of Obstetrics and Gynecology, Division of Reproductive Biology, Stanford University School of Medicine, Stanford, California 94305-5317. E-mail: aaron.hsueh{at}stanford.edu.

Recent studies indicated that ovarian functions are regulated by diverse paracrine factors induced by the preovulatory increases in circulating LH. Based on DNA microarray analyses and real-time RT-PCR, we found a major increase in the transcript levels of a chemokine fractalkine after human chorionic gonadotropin (hCG) treatment during the preovulatory period in gonadotropin-primed immature mice and rats. Although CX3CR1, the seven-transmembrane receptor for fractalkine, was also found in murine ovaries, its transcripts displayed minimal changes. Using tandem RT-PCR and immunohistochemistry, fractalkine transcripts and proteins were localized in cumulus, mural granulosa, and theca cells as well as the oocytes, whereas CX3CR1 was found in the same cells except the oocyte. Real-time RT-PCR further indicated the hCG induction of fractalkine transcripts in different ovarian compartments, with the highest increases found in granulosa cells. In cultured granulosa cells, treatment with fractalkine augmented hCG stimulation of progesterone but not estradiol and cAMP biosynthesis with concomitant increases in transcript levels for key steroidogenic enzymes (steroidogenic acute regulatory protein, CYP11A, and 3β-hydroxysteroid dehydrogenase). In cultured preovulatory follicles, treatment with fractalkine also augmented progesterone production stimulated by hCG. Furthermore, treatment with fractalkine augmented the phosphorylation of P38 MAPK in cultured granulosa cells. The present data demonstrated that increases in preovulatory LH/hCG induce the expression of fractalkine to augment the luteinization of preovulatory granulosa cells and suggest the fractalkine/CX3CR1 signaling system plays a potential paracrine/autocrine role in preovulatory follicles.