1,25-Dihydroxyvitamin D 3 Attenuates TSH and 8-(4-Chlorophenylthio)-cAMP-Stimulated Growth and Iodide Uptake by Rat Thyroid Cells (FRTL-5)

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 l,25-(OH)₂D₃ reduced the V _max of the sodium-driven iodide carriers to 30% of the control cells without effect on the K_m. Iodide efflux was only slightly increased in the 1,25-(OH)₂D₃-treated cells. In conclusion, l,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.