Jia Fang Wang

Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Thyroid growth and function are regulated by TSH in synergy with other hormones, growth factors, and neurotransmitters. Insulin-like growth factors (IGFs), which have insulin-like effects on metabolism and regulate cell growth and function, are synthesized and secreted by thyroid cells. IGFs are associated with their specific binding proteins (IGFBPs), which not only carry and store IGFs in body fluids but also modulate the biological function of IGFs. Previous studies found that both IGFs and IGFBPs participated in the regulation of the growth of thyroid cells.;This study has further examined the biological function of IGFs and IGFBPs in the regulation of the synthesis and secretion of thyroid hormones, using cultured sheep thyroid cells as an in vitro model. Both IGF-I and -II and IGFBPs were secreted by sheep thyroid cells. The release of IGFBP-2 and -5 was confirmed using Western blot analysis, while the release of IGFBP-3 was confirmed by physico-chemical criteria. IGF-I and -II potentiated the stimulatory effect of TSH on the synthesis and secretion of T{dollar}\sb4{dollar} and T{dollar}\sb3,{dollar} whereas this synergism of TSH with IGFs was inhibited by the addition of purified IGFBP-2. TSH did not significantly alter the secretion of IGF-I and -II, but significantly inhibited the secretion of IGFBPs. The inhibitory effect of TSH on IGFBP release was further enhanced by a combination of TSH, hydrocortisone, and insulin. Therefore, the synergistic effect of TSH with IGFs on the synthesis and secretion of thyroid hormones could be modulated by IGFBP presence under the control of TSH and other hormones. Furthermore, the secretion of IGFBPs was not altered when iodine uptake and organification was inhibited by supra-physiological concentrations of iodide, which inactivated TSH-dependent adenylate cyclase. The synthesis and secretion of IGFBPs were increased when the intracellular protein kinase C was activated. TSH inhibited the secretion of IGFBPs and inactivated protein kinase C, but simultaneously activated intracellular adenosine cyclase, which mediated the stimulation of the synthesis and secretion of thyroid hormones. Taken together, these results indicate that the interaction of TSH, IGFs, and IGFBPs contributes to the regulation of thyroid function.



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