(99m)Tc-labeled-rhTSH analogue (TR1401) for imaging poorly differentiated metastatic thyroid cancer.

Background: Differentiated thyroid carcinomas originating from thyroid follicular cells are frequent tumors of the thyroid with relatively good prognosis due to improved surgical techniques and follow-up procedures. Poorly differentiated thyroid cancers, which lose iodine uptake ability, in most cases still express thyrotropin (TSH) receptors (TSHR). Therefore, the aim of this study was to radiolabel a superagonist recombinant human TSH (rhTSH) analogue for imaging poorly differentiated thyroid cancer.

Effects of recombinant human thyroid-stimulating hormone superagonists on thyroidal uptake of 18F-fluorodeoxyglucose and radioiodide.

Background: Superagonist analogs of human thyroid-stimulating hormone (hTSH) may stimulate the uptake of (131)I-iodide and (18)F-fluorodeoxyglucose ((18)F-FDG) in thyroid carcinomas to a greater degree than hTSH. We herein report the potency and efficacy of two hTSH analogs, TR1401 and TR1402, to stimulate radioiodide and (18)F-FDG uptake in FRTL-5 cells and compared the effects of hTSH and TR1401 on radioiodide uptake in the thyroid in vivo in mice.

Methods: The effects of hTSH analogs on intracellular levels of cAMP, uptake of (131)I-iodide, and (18)F-FDG were studied in FRTL-5 cells to determine the stimulatory potency and efficacy of the compounds by calculating half-maximum effective concentration (EC(50)) values and maximal stimulatory effects (E(max)).

Regulation of uptake of 18F-FDG by a follicular human thyroid cancer cell line with mutation-activated K-ras.

Unlabelled: Dedifferentiation of thyroid carcinoma is accompanied by increased accumulation of the PET tracer (18)F-FDG. The molecular mechanisms responsible for this phenomenon are poorly understood. Therefore, we studied the regulation of (18)F-FDG uptake by the human follicular thyroid carcinoma cell line ML-1 and the as-yet-unknown oncogene expression of that cell line.

Human alpha-subunit analogs act as partial agonists to the thyroid-stimulating hormone receptor: differential effects of free and yoked subunits.

The alpha-subunit is common to the heterodimeric glycoprotein hormones and has been highly conserved throughout vertebrate evolution. In an effort to determine if wild-type and engineered human alpha analogs can serve as agonists or antagonists to the human thyroid-stimulating hormone (TSH) receptor (TSHR), a potent alpha mutant, obtained by replacing four amino acid residues with lysine (alpha4K), was assayed and compared with the wild-type alpha-subunit. When added to CHO cells expressing TSHR, alpha4K, and to a very limited extent the fused homodimer, alpha4K-alpha4K, but not alpha, exhibited agonist activity as judged by cAMP production.

Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships.

This review focuses on recent advances in the structure-function relationships of thyroid-stimulating hormone (TSH) and its receptor. TSH is a member of the glycoprotein hormone family constituting a subset of the cystine-knot growth factor superfamily. TSH is produced by the pituitary thyrotrophs and released to the circulation in a pulsatile manner.