RESUMO
Type 1 (D1) and 2 (D2) iodothyronine deiodinases are selenocysteine-containing enzymes that catalyze the deiodination of T4 to T3 in the thyroid and in peripheral tissues. Despite their importance to the plasma T3 pool in human beings, there are few studies about their behavior in human thyroids. In order to better understand iodothyronine deiodinase regulation in the thyroid gland, we studied thyroid tissue samples from follicular adenoma (AD, n = 5), toxic diffuse goiter (TDG, n = 6), nontoxic multinodular goiter (NMG, n = 40), papillary thyroid carcinoma (PTC, n = 8), and surrounding normal tissues (NT, n = 7) from 36 patients submitted to elective thyroidectomy. D1 and D2 activities were determined by quantification of the radioiodine released by ¹²5I-rT3 or ¹²5I-T4 under standardized conditions, and expressed as pmol rT3 deiodinated per minute and mg protein (pmol rT3 min⻹ mg⻹ ptn) and fmol T4 deiodinated per minute and mg protein (fmol T4 min⻹ mg⻹ ptn), respectively. D1 activity detected in TDG and AD tissues were significantly higher than in NT, PTC or NMG samples. D2 activity was also significantly higher in TDG and AD samples than in PTC, NMG, or NT. There was great variability in D1 and D2 enzymatic activities from distinct patients as well as from different areas from the same goiter. There was a positive correlation (P < 0,0001, r = 0.4942) between D1 and D2 activities when all samples were taken into account, suggesting that-in the thyroid-these two iodothyronine deiodinases may have related regulatory mechanisms, even if conditioned by other as yet unknown factors.
Assuntos
Bócio Nodular/enzimologia , Iodeto Peroxidase/metabolismo , Proteínas de Neoplasias/metabolismo , Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/enzimologia , Adenoma/enzimologia , Adenoma/patologia , Adolescente , Adulto , Idoso , Carcinoma/enzimologia , Carcinoma/patologia , Carcinoma Papilar , Feminino , Bócio/enzimologia , Bócio/patologia , Bócio Nodular/patologia , Humanos , Isoenzimas/metabolismo , Cinética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tamanho do Órgão , Câncer Papilífero da Tireoide , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem , Iodotironina Desiodinase Tipo IIRESUMO
Thyrotrophin induces proliferation and function in thyroid cells acting through a seven transmembrane G protein-coupled receptor. The proliferative pathways induced by thyrotropin (TSH) in thyrocytes in vivo are not completely understood yet. The aim of this work is to evaluate if Ras can be induced by TSH in rat thyroids, and whether extracellular regulated kinase (ERK) may be involved in the subsequent intracellular signalling cascade. We induced hypothyroidism in Wistar rats by methimazole (MMI) treatment (0.03% in the drinking water for 21 days). A subset of the hypothyroid rats received T4 (1 microg/100 g bw) during the last 10 days of MMI treatment. Hyperthyroidism was induced by subcutaneous injections of T4 (10 microg/100 g bw) during 10 days in another group of rats. Our data show that in the hypothyroid rats there is a clear positive Ras modulation, but a decrease in pERK. In contrast, thyroidal pERK increases in T4-induced hyperthyroidism, but without any change in RAS, although these changes did not reach statistical significance. Thus, while the rat thyroid proliferation induced by TSH may involve an increase in RAS signalling, the subsequent cascade does not involve ERK phosphorilation, which in fact, increases during T4-induced hyperthyroidism.
Assuntos
Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Sistema de Sinalização das MAP Quinases , Glândula Tireoide/patologia , Proteínas ras/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/patologia , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/patologia , Masculino , Metimazol , Tamanho do Órgão , Fosforilação , Ratos , Ratos Wistar , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Tireotropina/sangue , Tireotropina/farmacologia , TiroxinaRESUMO
Iodothyronine deiodinase activities are regulated by sex steroids; however, the mechanisms underlying the reported sexual dimorphism are poorly defined. In the present report, we aimed to investigate whether type 1 deiodinase (D1) sexual dimorphism exists early in sexual development by studying pre-pubertal male (Pm) and female (Pf) rats, as well as adult controls (C) and gonadectomized male and females rats. Adult male Wistar rats were studied 21 days after orchiectomy (Tex), and adult females were studied 21 days after ovariectomy (Ovx), and after estradiol benzoate (Eb) replacement. Serum total triiodothyronine (T3) was higher in pre-pubertal (P) rats than in the matching adults, with no difference between genders, although in adult males T3 was significantly lower than in females. There were no sex or age differences in serum total T4. Serum TSH in pre-pubertal (P) rats was within the adult female range, and both were significantly lower than in adult males. D1 activity in liver was greater in Pm than in Pf. In adult females, liver D1 activity was lower, while in adult males it was higher than in P rats. The same pattern of D1 activity was found in kidney. In thyroid and pituitary, D1 activity was similar in Pm, Pf, and adult females, which were all significantly lower than in the adult male. There were no differences in serum T3 and T4 between C and Tex males, but serum TSH was significantly decreased in Tex rats. Hepatic and renal D1 activities were lower in Tex than in C, but no changes were detected in thyroid and pituitary. In Ovx females, T3 was significantly lower than in the C group. Serum T4 was significantly decreased by estradiol replacement therapy in Ovx rats, in both doses used, whereas TSH was unchanged. Eb replacement increased liver and thyroid D1 activity, but in the kidney, only the highest estradiol dose promoted a significant D1 increase. In conclusion, in males, hepatic and renal D1 activity appears to be significantly influenced by gonadal hormones, in contrast to females, in which only exogenous Eb treatment stimulated D1 activity. The comparison between pre-pubertal and adult rats suggests that serum T3 is not the main regulator of D1 activity, and other factors, besides T3 and gonadal hormones, can modulate D1 activity during murine maturation.