Regulation of amino acid transport in rat and human thyroid cells

Abstract

To clarify the role of insulin, IGF-I and TSH in thyroid cell regulation, their effects on amino acid transport were studied separately. These effects were noted and compared using both the Wistar rat thyroid cell line and human thyroid cell cultures. Insulin, IGF-I and TSH were able independently to induce the radiolabelled \ g=a\ \ x=r eq-\ aminoisobutyric acid transport within the rat thyroid cells: TSH stimulated the amino acid transport in rat thyroid cells in a dose-dependent way from 1 pmol/l to 10 nmol/l. Similarly, insulin increased amino acid transport significantly from 0.17 nmol/1 up to 0.17 \g=m\mol/land IGF-I from 0.13 pmol/l up to 0.13 \g=m\mol/l.The combined effects of insulin and TSH on amino acid transport were equal to the theoretical sum of the activities, whereas those of IGF-I and TSH were greater than the theoretical one.When human thyroid cell cultures were used, a significant increase of labelled amino acid transport was induced by TSH, i.e. from 0.1 pmol/l to 10 pmol/l; IGF-I stimulated amino acid transport in a range from 0.13 pmol/l to 13 pmol/l, under the same conditions. Conversely, only large doses of insulin, i.e. 1.7 nmol/l, were able weakly to stimulate amino acid transport. When submaximal TSH and IGF-I doses were co-incubated in human thyroid cells, an additive effect on amino acid transport was observed.Insulin and insulin-like growth factor I are two re¬ lated peptides which play an important role in the growth and differentiation of several organs (1-8) including the thyroid gland (9-16). The existence of IGF-I receptors on thyroid cells in different species has recently been demonstrated ( 17-20). It has been postulated that IGF-I is involved in a paracrine mechanism oí action at the thyroid level (21). Strong evidence suggests that there is an autocrine secretion of IGF-I by ovine and human thyroid cells (17-19, 22,23).IGF-I and insulin potentiate the mitogenic ef¬ fects of TSH on FRTL-5 cells (9, 10), on Wistar rat thyroid cells (WRT cells, 24) and on human thyroid follicles in suspension culture (25). However, while insulin exerts the same effects on differentiated normal human thyroid cells (26), conflicting re¬ sults have been found as to the IGF-I mitogenic ef¬ fect in human thyroid cell monolayers (23,25). Since insulin is a mitogen which acts on the WRT cell line alone (24), the biological action of the pep¬ tides may vary according to species and ex¬ perimental models. The aim of this study was to examine further the role of insulin and IGF-I in regulating thyroid cell function under different conditions, on the as¬ sumption that the biological action of the peptides is not limited to the stimulation of cell prolifera¬ tion (3,8,(27)(28)(29)(30)(31)(32)(33). With this purpose, the single and combined effects of insulin, IGF-I, and TSH on a sodium-dependent, cyclohexamide-sensitive transport of radiolabelled a-aminoisobutyric acid were studied in WRT clonal cells and human thy¬ roid cells in primary culture.