Endocrinology, Vol 123, 1385-1394, Copyright © 1988 by Endocrine Society

ARTICLES

The effects of transforming growth factor-beta on growth and differentiation of the continuous rat thyroid follicular cell line, FRTL-5

JC Morris 3d, G Ranganathan, ID Hay, RE Nelson and NS Jiang
Division of Endocrinology and Internal Medicine, Mayo Clinic and Medical Center, Rochester, Minnesota 55905.

Transforming growth factor-beta (TGF beta) has been shown to influence the growth and differentiation of many widely varied cell types in vitro, including some that are endocrinologically active. We have investigated the previously unknown effects of this unique growth factor in the differentiated rat thyroid follicular cell line FRTL-5. The cells demonstrated specific, high affinity binding of TGF beta, and as with other epithelial cells, the growth of these thyroid follicular cells was potently inhibited by addition of TGF beta to the culture medium. TGF beta caused a significant reduction in TSH-sensitive adenylate cyclase activity in the cells. The addition of (Bu)2cAMP along with the growth factor to cultures partially reversed the characteristic morphological changes seen with TGF beta, but did not reverse the growth inhibition. To further investigate the possible mechanisms of the effects of TGF beta on the cells, we measured the influence of the growth factor on [125I]TSH binding. TGF beta did not compete for specific TSH-binding sites; however, exposure of the cells to TGF beta for 12 or more h resulted in a dose-dependent down- regulation of TSH receptors that was fully reversible. While cellular proliferation was potently inhibited by TGF beta, differentiated function, as manifest by iodine-trapping ability, was stimulated by the growth factor. This stimulation of iodine uptake was independent of, and additive to, the stimulatory effects of TSH. Finally, FRTL-5 cells in serum-free medium and in response to TSH were shown to secrete TGF beta-like activity that competed for [125I]TGF beta in a RRA. These studies suggest that TGF beta may represent an autocrine mechanism of controlling the growth response to TSH in thyroid follicular cells, while allowing the continuance of differentiated function.

This article has been cited by other articles:

				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]

				S. E. Matsuo, S. G. Leoni, A. Colquhoun, and E. T. Kimura Transforming growth factor-{beta}1 and activin A generate antiproliferative signaling in thyroid cancer cells. J. Endocrinol., July 1, 2006; 190(1): 141 - 150. [Abstract] [Full Text] [PDF]

				E. Costamagna, B. Garcia, and P. Santisteban The Functional Interaction between the Paired Domain Transcription Factor Pax8 and Smad3 Is Involved in Transforming Growth Factor-{beta} Repression of the Sodium/Iodide Symporter Gene J. Biol. Chem., January 30, 2004; 279(5): 3439 - 3446. [Abstract] [Full Text] [PDF]

				H. Ying, H. Suzuki, H. Furumoto, R. Walker, P. Meltzer, M. C. Willingham, and S.-Y. Cheng Alterations in genomic profiles during tumor progression in a mouse model of follicular thyroid carcinoma Carcinogenesis, September 1, 2003; 24(9): 1467 - 1479. [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]

				M. Eszlinger, K. Krohn, and R. Paschke Complementary DNA Expression Array Analysis Suggests a Lower Expression of Signal Transduction Proteins and Receptors in Cold and Hot Thyroid Nodules J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4834 - 4842. [Abstract] [Full Text] [PDF]

				H.-C. Kang, M. Ohmori, N. Harii, T. Endo, and T. Onaya Pax-8 Is Essential for Regulation of the Thyroglobulin Gene by Transforming Growth Factor-{beta}1 Endocrinology, January 1, 2001; 142(1): 267 - 275. [Abstract] [Full Text] [PDF]

				A. Franzén, E. Piek, B. Westermark, P. ten Dijke, and N.-E. Heldin Expression of Transforming Growth Factor-{beta}1, Activin A, and Their Receptors in Thyroid Follicle Cells: Negative Regulation of Thyrocyte Growth and Function Endocrinology, September 1, 1999; 140(9): 4300 - 4310. [Abstract] [Full Text]

				D Claisse, I Martiny, B Chaqour, Y Wegrowski, E Petitfrere, C Schneider, B Haye, and G Bellon Influence of transforming growth factor beta1 (TGF-beta1) on the behaviour of porcine thyroid epithelial cells in primary culture through thrombospondin-1 synthesis J. Cell Sci., January 5, 1999; 112(9): 1405 - 1416. [Abstract] [PDF]

				S. Toda, S. Matsumura, N. Fujitani, T. Nishimura, N. Yonemitsu, and H. Sugihara Transforming Growth Factor-{beta}1 Induces a Mesenchyme-Like Cell Shape without Epithelial Polarization in Thyrocytes and Inhibits Thyroid Folliculogenesis in Collagen Gel Culture Endocrinology, December 1, 1997; 138(12): 5561 - 5575. [Abstract] [Full Text] [PDF]