Endocrine Abstracts (2006) 11 P832

Insulin-like growth factor-1 counteracts 131I-induced thyroid stunning by stimulating the transcription of the sodium/iodide symporter (NIS)

M Nordén, C Johanson, S Tedelind, F Larsson, T Carlsson & M Nilsson

Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.

Thyroid stunning means reduced radioiodine uptake in thyroid tissue or tumour following a diagnostic 131I test dose. This may compromise subsequent 131I radiotherapy. Recently, we found that 131I inhibits iodide uptake in cultured thyroid cells at non-lethal absorbed doses. Here, we have investigated whether 131I irradiation affects the TSH-stimulated transcription of the sodium/iodide symporter (NIS) gene, and whether insulin-like growth factor-1 (IGF-1) previously known to stimulate iodide transport is able to prevent 131I-induced thyroid stunning.

Methods: Confluent pig thyrocytes grown in bicameral culture systems were single or co-stimulated with TSH (1 mU/ml) and IGF-1 (10 ng/ml) and simultaneously irradiated with 7.5 Gy 131I for 48 hours. pNIS mRNA was quantified by real-time RT-PCR using 18S as reference. Transepithelial (basal-to-apical) iodide transport was monitored using 125I- as tracer. [3H]Thymidine incorporation and total DNA content were also measured.

Results: TSH increased the NIS mRNA expression 35-50-fold after 2 days and onwards. In irradiated cells the NIS transcript level was reduced by 45% and 75% after 2 and 5 days, correlating with inhibited iodide transport. IGF-1 per se had a small and delayed stimulatory effect, but further enhanced the TSH-stimulated NIS expression and iodide transport 4-6-fold. Co-stimulation with IGF-1 fully prevented the inhibitory effect of 131I on both parameters. 131I blocked the IGF-1 stimulated DNA synthesis, ruling out that the protective effect of IGF-1 was caused by increased cell number.

Conclusions: 131I inhibits thyroidal iodide transport by blocking NIS mRNA expression. IGF-1 exerts a radioprotective effect by rescuing both NIS transcription and iodide transport in 131I-irradiated thyroid cells.

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