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The Effects of Transforming Growth Factor-β on Growth and Differentiation of the Continuous Rat Thyroid Follicular Cell Line, FRTL-5

Division of Endocrinology and Internal Medicine (J.C.M., I.D.H.) and the Department of Laboratory Medicine (G.R., R.E.N., N.S.J.), Mayo Clinic and Medical Center Rochester, Minnesota 55905

Address requests for reprints to: Dr. John C. Morris, Division of Endocrinology and Internal Medicine, Mayo Clinic and Medical Center, Rochester, Minnesota 55905.

Abstract

Transforming growth factor-β (TGFβ) 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 TGFβ, and as with other epithelial cells, the growth of these thyroid follicular cells was potently inhibited by addition of TGFβ to the culture medium. TGFβ 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 TGFβ, but did not reverse the growth inhibition. To further investigate the possible mechanisms of the effects of TGFβ on the cells, we measured the influence of the growth factor on [¹²⁵I]TSH binding. TGFβ did not compete for specific TSH-binding sites; however, exposure of the cells to TGFβ for 12 or more h resulted in a dosedependent down-regulation of TSH receptors that was fully reversible. While cellular proliferation was potently inhibited by TGFβ, 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 TGFβ-like activity that competed for [¹²⁵I]TGFβ in a RRA. These studies suggest that TGFβ may represent an autocrine mechanism of controlling the growth response to TSH in thyroid follicular cells, while allowing the continuance of differentiated function. (Endocrinology 123: 1385–1394, 1988)

Received March 15, 1988.

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