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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0250v1 199/2/191    most recent Alert me when this article is cited Alert me if a correction is posted Services 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 Lee, E. J. Articles by Kim, J. M. Search for Related Content PubMed PubMed Citation Articles by Lee, E. J. Articles by Kim, J. M.

E Lee, Endocrinology, Yonsei University College of Medicine, Seoul, 120-752, Korea, Republic of
Y Lee, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, Republic of
J Kim, Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Korea, Republic of

Correspondence: Eun Jig Lee, Email: ele423{at}northwestern.edu

Abstract

The interaction of chemokine stromal cell-derived factor-1 (SDF1) and its receptor CXCR4 may play an important role in the regulation of anterior pituitary function. In this study, we investigated the expression of SDF1 and CXCR4 and their role in normal rat pituitary and growth hormone (GH)-producing GH3 tumor cell line. RT-PCR analysis and immunohistochemistry revealed that CXCR4 was expressed in normal rat anterior pituitary and GH3 tumor cells. Double immunofluorescent staining showed the complete colocalization of CXCR4 with growth hormone (GH) in rat pituitary, indicating that CXCR4 is specifically expressed in rat somatotrophs. Using rat primary pituitary cell cultures and GH releasing hormone receptor expressing stable GH3 cells (GH3-GHRHR), we evaluated the function of SDF1 compared to GHRH. SDF1 stimulated GH gene activation in both primary rat anterior pituitary cells, and GH3-GHRHR cells. SDF1 also stimulated GH secretion from primary rat pituitary cells in a dose-dependant manner. BrdU incorporation was increased in response to SDF1 addition in GH3 cell culture, indicating SDF1-induced cell proliferation. SDF1-dependent phosphorylation of ERK1/2 was also confirmed by Western blot analysis, supporting the evidence that MAPK is an intracellular mediator of SDF1/CXCR4 interaction in GH3 cell proliferation. In conclusion, these results indicate that SDF1/CXCR4 interaction plays an important role in GH production, secretion and the proliferation of somatotrophs.