RESUMO
Until recently, 3,5-diiodothyronine (3,5-T(2)) has been considered an inactive by-product of triiodothyronine (T(3)) deiodination. However, studies from several laboratories have shown that 3,5-T(2) has specific, nongenomic effects on mitochondrial oxidative capacity and respiration rate that are distinct from those due to T(3). Nevertheless, little is known about the putative genomic effects of 3,5-T(2). We have previously shown that hyperthyroidism induced by supraphysiological doses of 3,5-T(2) inhibits hepatic iodothyronine deiodinase type 2 (D2) activity and lowers mRNA levels in the killifish in the same manner as T(3) and T(4), suggesting a pretranslational effect of 3,5-T(2) (Garcia-G C, Jeziorski MC, Valverde-R C, Orozco A. Gen Comp Endocrinol 135: 201-209, 2004). The question remains as to whether 3,5-T(2) would have effects under conditions similar to those that are physiological for T(3). To this end, intact killifish were rendered hypothyroid by administering methimazole. Groups of hypothyroid animals simultaneously received 30 nM of either T(3), reverse T(3), or 3,5-T(2). Under these conditions, we expected that, if it were bioactive, 3,5-T(2) would mimic T(3) and thus reverse the compensatory upregulation of D2 and tyroid receptor beta1 and downregulation of growth hormone that characterize hypothyroidism. Our results demonstrate that 3,5-T(2) is indeed bioactive, reversing both hepatic D2 and growth hormone responses during a hypothyroidal state. Furthermore, we observed that 3,5-T(2) and T(3) recruit two distinct populations of transcription factors to typical palindromic and DR4 thyroid hormone response elements. Taken together, these results add further evidence to support the notion that 3,5-T(2) is a bioactive iodothyronine.
Assuntos
Di-Iodotironinas/farmacologia , Fundulidae/fisiologia , Hormônio do Crescimento/sangue , Iodeto Peroxidase/metabolismo , Glândula Tireoide/fisiologia , Receptores beta dos Hormônios Tireóideos/metabolismo , Animais , Di-Iodotironinas/sangue , Regulação Enzimológica da Expressão Gênica/fisiologia , Hipertireoidismo/metabolismo , Hipertireoidismo/fisiopatologia , Hipotireoidismo/metabolismo , Hipotireoidismo/fisiopatologia , Iodeto Peroxidase/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Elementos de Resposta/fisiologia , Glândula Tireoide/efeitos dos fármacos , Regulação para Cima/fisiologia , Iodotironina Desiodinase Tipo IIRESUMO
Estudos recentes com pacientes deprimidos têm evidenciado a presença de perturbaçöes no eixo hipotálamo-hipófise-tireoideo (HDT) e esta tem sido uma área para a qual os estudiosos do assunto têm dirigido seus esforços de pesquisa. Entre as alteraçöes mais freqüentes temos a diminuiçäo da resposta do hormônio estimulante da tireóide (TSH) à diminuiçäo da resposta do hormônio liberador da tireotropina (TRH). Foi demosntrado ainda que a triiodotironina (T3) aumenta os efeitos dos antidepressivos tricíclicos. Os autores fazem revisäo bibliográfica das alteraçöes neuroendócrinas presentes nos transtornos do humor, com foco no eixo HPT e depressäo