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Thyroid gland function and growth in IGF binding protein-1 transgenic mice
T Modric1, K Rajkumar, L J Murphy
1Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3.
European Journal of Endocrinology
|July 31, 1999
Summary
Overexpression of Insulin-like Growth Factor Binding Protein-1 (IGFBP-1) in mice led to increased thyroid growth in vivo, despite reduced IGF-I action in vitro. This suggests complex regulatory roles of IGFBP-1 in thyroid function.
Area of Science:
- Endocrinology
- Molecular Biology
- Thyroid Research
Background:
- Insulin-like Growth Factor-I (IGF-I), its receptor, and IGF-binding proteins (IGFBPs) are crucial for thyroid gland function and growth.
- IGFBP-1 specifically modulates IGF-I action, influencing cellular processes within the thyroid.
Purpose of the Study:
- To investigate the in vivo and in vitro effects of elevated IGFBP-1 levels on thyroid gland function and growth.
- To elucidate the role of IGFBP-1 in regulating thyroid hormone production and cellular proliferation.
Main Methods:
- Utilized transgenic mice with constitutive overexpression of IGFBP-1, exhibiting partial inhibition of IGF-I action.
- Assessed thyroid growth, morphology, and hormonogenesis in response to goitrogens (sodium perchlorate, methimazole).
- Evaluated in vitro thyroid follicle proliferation stimulated by IGF-I and Thyroid Stimulating Hormone (TSH).
Main Results:
- Transgenic mice showed increased relative thyroid weight but reduced serum thyroid hormones (T3, thyroxine) and T3-binding capacity.
- Goitrogen-induced thyroid growth was attenuated in transgenic mice, despite higher TSH levels, indicating altered responsiveness.
- In vitro, thyroid follicle proliferation response to IGF-I was diminished in transgenic mice, while TSH response remained unaffected.
Conclusions:
- Overexpression of IGFBP-1 attenuates IGF-I action in vitro but paradoxically enhances thyroid growth in vivo.
- These findings suggest IGFBP-1 influences thyroid function at multiple levels, leading to complex growth and functional outcomes.
- IGFBP-1 plays a significant role in modulating thyroid gland homeostasis and response to stimuli.