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¹ Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Otfried-Muellerstrasse 10, D-72076 Tuebingen, Germany
² Medical Centre of Postgraduate Education, Department of Biochemistry, Marymoncka 99, Pl-01-813 Warsaw, Poland

(Requests for offprints should be addressed to R Wahl; Email: richard.wahl{at}med.uni-tuebingen.de)

Retinoids are potential candidates for the treatment of thyroid cancer. However, one of the disadvantages of these substances is their dedifferentiating effect on normal non-transformed thyrocytes. To identify conditions under which no dedifferentiating effect of retinol on normal thyrocytes can be observed, we determined iodide uptake, protein iodination, expression of sodium–iodide symporter (NIS) mRNA and protein, and the binding of iodine-125-labelled bTSH in cultured porcine thyrocytes. Combination of TSH and 6.5 µM retinol increased iodide uptake and protein iodination compared with TSH alone over the entire incubation time, whereas TSH plus 13 µM retinol increased the uptake of iodine-125 only during the first 12 h but decreased it after 30 h and longer. After 30 h incubation times with 13 µM retinol, the fraction of apoptotic cells was enhanced and proliferation decreased. The incubation with retinol enhanced the binding of [¹²⁵I]bTSH to thyrocytes, but did not influence expression of the NIS. With low retinol concentrations, the effect on the binding of TSH apparently predominated and retinol increased thyroid function; with higher concentrations the pro-apoptotic effect of retinol overlapped and a two-phased time course resulted. It can be concluded that low concentrations of retinol also exert differentiating effects in normal thyrocytes.