Tie-2 is expressed on thyroid follicular cells, is increased in colter, and is regulated by thyrotropin through cyclic adenosine 3 ',5 '-monophosphate

Angiogenesis is coordinated with follicular cell growth in goitrogenesis. T he angiopoietins, Ang-1 and Ang-2, are angiogenic growth factors acting thr ough Tie-2, a tyrosine kinase receptor. We have examined the expression and regulation of the angiopoietins and Tie-2 in human and rat thyroids. In hu man goiters there was increased Tie-2 immunostaining, compared with that in normal thyroids, on both follicular and endothelial cells. In an induced g oiter in rats, in situ hybridization showed increased expression of messeng er ribonucleic acids (mRNAs) for Tie-2 and Ang-1 in follicular cells. As Ti e-2 has previously been believed to be restricted to cells of endothelial l ineage in adults, we examined its expression further in isolated follicular cells. Tie-2 and Ang-1 mRNA expression in human thyrocytes was confirmed b y ribonuclease protection assay. Ang-2 mRNA was not detected in human cultu res or rat thyroids. In both human follicular cell cultures and FRTL-5 cell s, immunoblotting showed that Tie-2 expression was increased by TSH and age nts that increased intracellular cAMP. In conclusion, we have demonstrated the expression of Tie-2 and Ang-1 in thyroid epithelial and endothelial cel ls, and have shown the regulation of Tie-2 by TSH and cAMP in follicular ce lls. Tie-2 expression is increased in goiter in both humans and rats, consi stent with a role in goitrogenesis.