Thyroid gland function and growth in IGF binding protein-1 transgenic mice.
OBJECTIVE
IGF-I, IGF-I receptor and IGF-binding proteins (IGFBPs) are expressed 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 increased IGFBP-1 levels on the function and growth of the thyroid gland.


METHODS
Transgenic mice which constitutively overexpress IGFBP-1 were used. These mice have a phenotype consistent with partial inhibition of IGF-I action.


METHODS
Thyroid growth, morphology and hormonogenesis were determined in transgenic mice treated with goitrogens, sodium perchlorate and methimazole. In 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 wild-type. While an inverse relationship between T(3) and TSH was observed in both groups of goitrogen-treated mice, the slope of the line of best fit was less steep in transgenic mice compared 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 isolated thyroid follicles to IGF-I, but not to TSH, was reduced in transgenic, compared with wild-type mice.


CONCLUSIONS
The results of this study suggest that, while overexpression of IGFBP-1 attenuates IGF-I action in vitro, it enhances thyroid growth in vivo, presumably as a result of perturbations in thyroid function at multiple levels.
Modric
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Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3.
Rajkumar
K
K
Murphy
L J
LJ
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D013956:Antithyroid Agents; D002455:Cell Division; D004195:Disease Models, Animal; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D066298:In Vitro Techniques; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008713:Methimazole; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D010472:Perchlorates; D017670:Sodium Compounds; D013961:Thyroid Gland / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D013963:Thyroid Hormones / Q000096:biosynthesis*; D015854:Up-Regulation
D013956:Antithyroid Agents; D018970:Insulin-Like Growth Factor Binding Protein 1; D010472:Perchlorates; D017670:Sodium Compounds; D013963:Thyroid Hormones; D008713:Methimazole; D007334:Insulin-Like Growth Factor I; C031068:sodium perchlorate