Low TSH requirement and goiter in transgenic mice overexpressing IGF-I and IGF-Ir receptor in the thyroid gland.
Through the cAMP signaling pathway, TSH stimulates thyroid follicular cell proliferation, differentiation, and function. Although the autocrine production of IGF-I in the thyroid gland suggests an important physiological function for this factor in these processes, the exact role of the IGF-I/IGF-I receptor system in vivo remains unclear. Although the mitogenic action of TSH requires the presence of IGF-I or insulin in primary culture of dog and human thyroid cells, IGF-I has an effect equal to and independent of the effect of TSH on cell proliferation in rat thyroid cell lines and may even be the main growth regulator in this case. To investigate the in vivo function of the IGF-I/IGF-I receptor system, transgenic mice overexpressing human IGF-I, IGF-I receptor, or both in the thyroid were generated. Adult transgenic mice did not present external signs of thyroid dysfunction, but mice overexpressing both transgenes had significantly increased gland weight and follicular lumen area. A decreased TSH level together with a slightly increased serum T(4) concentration and increased thyroidal iodine uptake were also observed, suggesting that IGF-I and IGF-I receptor stimulate thyroid function to some extent in vivo.
Clément
S
S
Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Institut de Biologie et de Médecine Moléculaire, Université Libre de Bruxelles, 6041 Gosselies, Belgium. sclement@ulb.ac.be
Refetoff
S
S
Robaye
B
B
Dumont
J E
JE
Schurmans
S
S
D000818:Animals; D006042:Goiter / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007455:Iodine / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009929:Organ Size; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013972:Thyrotropin / Q000097:blood / Q000502:physiology*; D013974:Thyroxine / Q000097:blood
D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D007455:Iodine; D017526:Receptor, IGF Type 1; D013974:Thyroxine