This Article Full Text Full Text (PDF) All Versions of this Article: 146/5/2473    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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Park, Y. J. Articles by Park, D. J. Search for Related Content PubMed PubMed Citation Articles by Park, Y. J. Articles by Park, D. J.

p66Shc Expression in Proliferating Thyroid Cells Is Regulated by Thyrotropin Receptor Signaling

Department of Internal Medicine (Y.J.P., T.Y.K., S.H.L, S.W.K., B.Y.C., D.J.P.) and General Surgery (Y.K.Y), Seoul National University College of Medicine, Seoul 110-799; Department of Internal Medicine (Y.J.P), Seoul National University Bundang Hospital, Seongnam 463-707; Clinical Research Institute (B.Y.C., D.J.P.), Seoul National University Hospital, Seoul 110-744; Department of Internal Medicine (H.K., M.S.), School of Medicine, Chungnam National University, Taejon 301-747; and Thyroid Cancer Clinic (S.W.K), National Cancer Center, Goyang 411-769 Korea

Address all correspondence and requests for reprints to: Do Joon Park, M.D., Ph.D., Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong Chongno-gu, Seoul 110-744, Korea. E-mail: djpark{at}snu.ac.kr.

It is almost unanimously accepted that thyrocyte proliferation is synergistically activated by TSH and insulin/IGF-I. Moreover, it was recently suggested that p66Shc, which is an adaptor molecule of the IGF-I receptor, might play a critical role in this synergistic effect. In this study, we undertook to confirm the role and the mechanism underlying the regulation of p66Shc expression via TSH receptor in thyrocytes. We have found that p66Shc expression is elevated in proliferating human thyroid tissues, including adenomatous goiter, adenoma, Graves’ disease, and thyroid cancer, but not in normal thyroid. Among growth factors, TSH increased p66Shc expression both in vivo and in vitro; however, IGF-I, epidermal growth factor, or insulin did not. TSH and Graves’ Ig increased the p66Shc expression via the TSH receptor-G_s-cAMP pathway. However, interestingly, IGF-I or epidermal growth factor increased the tyrosine phosphorylations of p66Shc, and this was enhanced by TSH pretreatment. A similar synergism was observed during the DNA synthesis. When we measured the p66Shc levels induced by individual Igs from 130 patients with Graves’ disease, TSH receptor stimulating activity and goiter size showed a weak correlation. We conclude that the expression of p66Shc is regulated by signaling through the TSH receptor in proliferating thyroid cells and that p66Shc appears to be an important mediator of the synergistic effect between TSH and IGF-I with respect to thyrocyte proliferation. Moreover, we suggest that TSH potentiates the regulatory effect of IGF-I on thyrocyte growth, at least in part, by increasing the expression of p66Shc.

This article has been cited by other articles:

				H. A. Drexhage Are There More than Antibodies to the Thyroid-Stimulating Hormone Receptor that Meet the Eye in Graves' Disease? Endocrinology, January 1, 2006; 147(1): 9 - 12. [Full Text] [PDF]