1,25-Dihydroxyvitamin D3Attenuates TSH and 8-(4-Chlorophenylthio)-cAMP-Stimulated Growth and Iodide Uptake by Rat Thyroid Cells (FRTL-5)

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Abstract
The effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on TSH and the 3',5'-cyclic adenosine monophosphate (cAMP) analogue 8-(4-chlorophenylthio)-cAMP-stimulated cell growth and iodide uptake were studied in a rat thyroid cell line (FRTL-5). 1,25-(OH)2D3 inhibited both TSH and 8-(4-chlorophenylthio)-cAMP-induced cell proliferation with the maximum effect at 100 nmol/L. The inhibitory effect of 1,25-(OH)2D3 (10 nmol/L) on TSH and 8-(4-chlorophenylthio)-cAMP-stimulated iodide uptake was observed after 2 days of incubation, and the effect was maximal after 4 days. The inhibition was dose-dependent and maximal at 100 nmol/L 1,25-(OH)2D3. 1,25-(OH)2D3 (10 nmol/L, 4 days) increased the median concentrations of TSH required to stimulate both cAMP production and iodide uptake half-maximally by 124 and 187%, respectively, whereas the median 8-(4-chlorophenylthio)-cAMP concentration was not changed. Lineweaver-Burke plots revealed that 1,25-(OH)2D3 reduced the Vmax of the sodium-driven iodide carriers to 30% of the control cells without effect on the Km. Iodide efflux was only slightly increased in the 1,25-(OH)2D3-treated cells. In conclusion, 1,25-(OH)2D3 potently inhibited the TSH-stimulated growth and iodide uptake by FRTL-5 cells both by reducing the TSH-stimulated cAMP production and by attenuating the stimulatory effects of cAMP.