HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Burikhanov, R. Articles by Roger, P. P. Search for Related Content PubMed PubMed Citation Articles by Burikhanov, R. Articles by Roger, P. P. Social Bookmarking                      What's this?

Volume 271, Number 46, Issue of November 15, 1996 pp. 29400-29406
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Thyrotropin via Cyclic AMP Induces Insulin Receptor Expression and Insulin Co-stimulation of Growth and Amplifies Insulin and Insulin-like Growth Factor Signaling Pathways in Dog Thyroid Epithelial Cells

(Received for publication, June 6, 1996, and in revised form, July 29, 1996)

From the Institute of Interdisciplinary Research, Université Libre de Bruxelles, Campus Erasme, 1070 Brussels, Belgium

Despite the similarity of their receptors and signal transduction pathways, insulin is regarded as a regulator of glucose, protein, and lipid metabolism, whereas insulin-like growth factors (IGF-I and IGF-II) mainly act as mitogenic hormones. In the dog thyroid primary culture model, the triggering of DNA synthesis by thyrotropin (TSH) through cAMP, or by cAMP-independent factors including epidermal growth factor, hepatocyte growth factor and phorbol esters, requires insulin or IGFs as comitogenic factors. In the present study, in TSH-treated cells, IGF-I receptors and insulin receptors were paradoxically equivalent in their capacity to elicit the comitogenic pathway, which, however, was mediated only by IGF-I receptors in dog thyroid cells stimulated by cAMP-independent mitogens. Moreover, prior cell exposure to TSH or forskolin increased their responsiveness to insulin, IGF-I, and IGF-II, as seen on DNA synthesis and activation of a common insulin/IGF signaling pathway. To understand these observations, binding characteristics and expression of insulin and IGF-I receptors were examined. To analyze IGF-I receptor characteristics, the unexpected interference of a huge presence of IGF-binding proteins at the cell membrane was avoided using labeled Long R³ IGF-I instead of IGF-I. Strikingly, TSH, through cAMP, time-dependently induced insulin binding and insulin receptor mRNA and protein accumulation without any effect on IGF-I receptors. These findings constitute a first example of an induction of insulin receptor gene expression by a cAMP-mediated hormone. In dog thyroid cells, this allows low physiological insulin concentrations to act as a comitogenic factor and might explain in part the enhanced responsiveness to IGFs in response to TSH. This raises the possibility that TSH-insulin interactions may play a role in the regulation of thyroid growth and function in vivo.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. J. Costa, M. Senou, F. Van Rode, J. Ruf, M. Capello, D. Dequanter, P. Lothaire, C. Dessy, J. E. Dumont, M.-C. Many, et al. Reciprocal Negative Regulation between Thyrotropin/3',5'-Cyclic Adenosine Monophosphate-Mediated Proliferation and Caveolin-1 Expression in Human and Murine Thyrocytes Mol. Endocrinol., April 1, 2007; 21(4): 921 - 932. [Abstract] [Full Text] [PDF]

				S. Paternot, J. E. Dumont, and P. P. Roger Differential Utilization of Cyclin D1 and Cyclin D3 in the Distinct Mitogenic Stimulations by Growth Factors and TSH of Human Thyrocytes in Primary Culture Mol. Endocrinol., December 1, 2006; 20(12): 3279 - 3292. [Abstract] [Full Text] [PDF]

				M. J. Costa, Y. Song, P. Macours, C. Massart, M. C. Many, S. Costagliola, J. E. Dumont, J. Van Sande, and V. Vanvooren Sphingolipid-Cholesterol Domains (Lipid Rafts) in Normal Human and Dog Thyroid Follicular Cells Are Not Involved in Thyrotropin Receptor Signaling Endocrinology, March 1, 2004; 145(3): 1464 - 1472. [Abstract] [Full Text] [PDF]

				J.-C. Goffard, L. Jin, H. Mircescu, P. Van Hummelen, C. Ledent, J.-E. Dumont, and B. Corvilain Gene Expression Profile in Thyroid of Transgenic Mice Overexpressing the Adenosine Receptor 2a Mol. Endocrinol., January 1, 2004; 18(1): 194 - 213. [Abstract] [Full Text] [PDF]

				S. Clement, S. Refetoff, B. Robaye, J. E. Dumont, and S. Schurmans Low TSH Requirement and Goiter in Transgenic Mice Overexpressing IGF-I and IGF-I Receptor in the Thyroid Gland Endocrinology, December 1, 2001; 142(12): 5131 - 5139. [Abstract] [Full Text] [PDF]

				T. Kimura, A. Van Keymeulen, J. Golstein, A. Fusco, J. E. Dumont, and P. P. Roger Regulation of Thyroid Cell Proliferation by TSH and Other Factors: A Critical Evaluation of in Vitro Models Endocr. Rev., October 1, 2001; 22(5): 631 - 656. [Abstract] [Full Text] [PDF]

				K. Krohn and R. Paschke Progress in Understanding the Etiology of Thyroid Autonomy J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3336 - 3345. [Full Text] [PDF]

				A. Van Keymeulen, S. Deleu, J. Bartek, J. E. Dumont, and P. P. Roger Respective Roles of Carbamylcholine and Cyclic Adenosine Monophosphate in Their Synergistic Regulation of Cell Cycle in Thyroid Primary Cultures Endocrinology, March 1, 2001; 142(3): 1251 - 1259. [Abstract] [Full Text] [PDF]

				M. Derwahl, M. Broecker, and Z. Kraiem Thyrotropin May Not Be the Dominant Growth Factor in Benign and Malignant Thyroid Tumors J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 829 - 834. [Full Text]

				F. Depoortere, A. Van Keymeulen, J. Lukas, S. Costagliola, J. Bartkova, J. E. Dumont, J. Bartek, P. P. Roger, and S. Dremier A Requirement for Cyclin D3-Cyclin-dependent Kinase (cdk)-4 Assembly in the Cyclic Adenosine Monophosphate-dependent Proliferation of Thyrocytes J. Cell Biol., March 23, 1998; 140(6): 1427 - 1439. [Abstract] [Full Text] [PDF]