One of the distinguishing characteristics of the thyroid follicular cell is its i ability to concentrate iodide, and iodide uptake is one of the main parameters used in determining the level of metabolic function of normal and tumorigenic thyroid tissue. Iodide transport can be considered the first step in thyroid hormone biosynthesis, and is tightly regulated by TSH. Evidence suggests that one of the responses of the thyroid cell to TSH may be de novo synthesis of transporter mRNA and/or protein. Additionally, iodide transport is regulated by serum iodide levels, although the mechanism underlying this regulation is controversial. Iodide also regulates the growth of thyroid cells, perhaps by potentiating their response to TSH. Consequently, identification and a more detailed understanding of the iodide transporter would provide a great deal of information about the regulation of thyroid function in normal and diseased thyroid tissue. Research on the thyroid iodide transporter will be initiated with experiments designed to isolate a cDNA encoding the transporter, using expression of mRNA in Xenopus oocytes as a bioassay. A complete cDNA clone of the transporter will be generated, and used to examine the regulation of the iodide transporter mRNA in response to TSH and iodide. Polyclonal antibodies, generated against peptides synthesized based on the deduced amino acid sequence of the transporter, will be used to identify the iodide transporter protein. The protein structure and the regulation of the protein in response to TSH and iodide will also be examined. Ultimately, the iodide transporter will be used as a tool for understanding, on a molecular level, how the cAMP signal transduction pathway controls thyroid cell growth and the coordinate expression of thyroid specific gene products required for thyroid hormone biosynthesis.
| Tsuzaki, S; Cone, R D; Frazier, A L et al. (1991) The interaction of signal transduction pathways in FRTL5 thyroid follicular cells: studies with stable expression of beta 2-adrenergic receptors. Endocrinology 128:1359-68 |
| Frazier, A L; Robbins, L S; Stork, P J et al. (1990) Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing. Mol Endocrinol 4:1264-76 |
