Mechanisms Involved In Tri-iodothyronine (T3) Formation

CINTIA E. CITTERIO; PETER ARVAN

Ann Arbor

Simposio; Brehm/Kellogg Trainee Symposium 2016; 2016

Kellogg Eye Center, University of Michigan, Estados Unidos

In two common thyroid diseases ? hypothyroidism caused by iodine deficiency, and autoimmune hyperthyroidism (Graves? disease) ? a central mechanism includes massive hyperstimulation of thyrocytes by Thyroid Stimulating Hormone (TSH). Interestingly, both conditions result in increased T3 relative to T4 production in the thyroid gland. In this study, we have investigated the hypothesis that in thyrocytes hyperstimulated by TSH, the structure of the TG may be altered to favor chemical coupling of residues involved in T3 formation. We treated PCCl3 thyrocytes with lower and hyperstimulating concentrations of TSH and collected secreted TG. To examine the ability of secreted TG to form de novo T3 within its structure, we performed iodination in vitro followed by Western blotting with monoclonal anti-T3 antibodies. Alternatively, we added a TSH receptor-stimulating antibody (KSAb1) that mimics Graves? disease. To validate our method, we analyzed new T3 formation within TG from mice hyperstimulated by TSH and mice with genetic deletion of TSH receptors. Altogether, we found that TG synthesized in thyrocytes stimulated by TSH is intrinsically more capable of de novo T3 formation. Moreover, we found that T3 formation occurs at special sites within the carboxyl-terminal region of TG.