Thyroid gland function and growth in IGF binding protein-1 transgenic mice

Objective: IGF-I, IGF-I receptor and IGF-binding proteins (IGFBPs) are expr essed in thyroid tissue and are associated with the function and growth of the thyroid. This study investigated the in vivo and in vitro effects of in creased IGFBP-1 levels on the function and growth of the thyroid gland. Design: Transgenic mice which constitutively overexpress IGFBP-1 were used. These mice have a phenotype consistent with partial inhibition of IGF-I ac tion. Methods: Thyroid growth, morphology and hormonogenesis were determined in t ransgenic mice treated with goitrogens, sodium perchlorate and methimazole. Pn vitro cell proliferation in thyroid follicles was assessed in response to IGF-I and TSH. Results: Thyroid weight was increased in transgenic mice, relative to their body mass, whereas serum tri-iodothyronine (T-3) thyroxine and T-3-binding capacity were reduced, compared with wildtype. While an inverse relationsh ip between T-3 and TSH was observed in both groups of goitrogen treated mic e, the slope of the line of best fit was less steep in transgenic mice comp ared with wild-type mice. Thyroid growth was less marked in transgenic than wild-type mice in response to goitrogens, although TSH levels were higher in goitrogen-treated transgenics. In vitro proliferative response of isolat ed thyroid follicles to IGF-I, but not to TSH, was reduced in transgenic, c ompared with wild-type mice. Conclusions: The results of this study suggest that, while overexpression o f IGFBP-1 attenuates IGF-I action ill vitro, it enhances thyroid growth in vivo, presumably as a result of perturbations in thyroid function at multip le levels.