Expressão das iodotironinas desiodases nas neoplasias tireoidianas

Abstract

RESUMOAs iodotironinas desiodases formam uma família de selenoenzimas com propriedades catalíticas distintas que ativam ou inativam os hormônios tireoidianos via desiodação do anel fenólico ou tirosínico da molécula do T4. As desiodases tipo I e II (D1 e D2) são as enzimas responsáveis pela geração do T3 e são amplamente expressas na tireóide normal. A transformação neoplásica benigna ou maligna da glândula tireóide está associada a alterações na expressão dessas isoenzimas, sugerindo um possível papel da D1 e da D2 como marcadores de diferenciação celular. Anormalidades na expressão de ambas enzimas e da desiodase tipo III (D3), inativadora do hormônios tireoidianos, são também encontradas em outras neoplasias humanas. Os mecanismos ou implicações do aumento ou diminuição das desiodases na patogênese neoplásica são pouco compreendidas. No entanto, é importante observar que a expressão anormal da D2 pode ser responsável por um quadro de tireotoxicose em pacientes com metástases de carcinoma folicular de tireóide, enquanto que o aumento da D3 em hemangiomas pode causar hipotireoidismo de difícil tratamento. The iodothyronine deiodinases constitute a family of selenoenzymes that catalyze the removal of iodine from the outer ring or inner ring of the thyroid hormones. The activating enzymes, deiodinases type I (D1) and type II (D2), are highly expressed in normal thyroid gland. Benign or malignant neoplastic transformation of the thyroid cells is associated with changes on the expression of these enzymes, suggesting that D1 or D2 can be markers of cellular differentiation. Abnormalities on the expression of both enzymes and also of the deiodinase type III (D3), that inactivates thyroid hormones, have been found in other human neoplasias. So far, the mechanism or implications of these findings on tumor pathogenesis are not well understood. Nevertheless, it's noteworthy that abnormal expression of D2 can cause thyrotoxicosis in patients with metastasis of follicular thyroid carcinoma and that increased D3 expression in large hemangiomas causes severe hypothyroidism.

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

“…In contrast, type 3 iodothyronine deiodinase (DIO3, D3) catalyzes the inactivation of T 4 and T 3 via inner ring deiodination . Several studies have shown an association between thyroidal status and tumor pathogenesis (Pinto et al 2011, Kim & Cheng 2013 while several reports have documented changes in the expression of deiodinases in benign and malignant tumors (Huang et al 2001, Murakami et al 2001, de Souza Meyer et al 2005, Dentice et al 2007, Meyer et al 2007.…”

Thyroid Hormone Deiodinases and Cancer

“…Notably, a growing number of studies indicate that deiodinase expression is also altered in cancer (previously reviewed in Meyer et al, 2007; Piekielko-Witkowska and Nauman, 2011). While it is conceivable that deiodinase expression is unrelated to the cancer process, there is good indication that deiodinase reactivation could in some cases constitute a useful marker of the disease (Gereben and Bianco, 2009; Piekielko-Witkowska et al, 2009).…”

Type 2 iodothyronine deiodinase is highly expressed in medullary thyroid carcinoma

“…Abnormal D2 expression and function have been described previously in other human neoplasms (Curcio et al, 2001;Dentice et al, 2007;Meyer et al, 2007;Morimura et al, 2005). Indeed, it is conceivable that thyroid status is linked to the development and growth of neoplastic tissues (Lemaire et al, 1981;Leuthauser et al, 1987).…”