Effect of 3,5,3-triiodo-L thyronine supplementation on the cerebral neurotransmitters in hypothyroid rat offspring

Nervous system growth and differentiation are intimately interrelated with the presence of thyroid hormones [THs] in early development stages. Hypothyroidism during the fetal and postnatal life results in an irretrievable mental retardation syndrome. Assessment of the effect of 3,5,3- triiodo-L-thyronine [T[3]] on changes in the cerebral neurotransmitters level and its possible mechanism in hypothyroid rat male offspring. Hypothyroidism during pregnancy and lactation in one group [hypothyroid group] was performed by antithyroid drug, methimazole [MMI] that was added in drinking water at concentration 0.02%. Another group [T[3]-treated hypothyroid group] MMI was stopped and animal's offspring were received T[3] [20 micro g/100 g body weight in 0.01 N NaOH, i.p.] for one week. The third group is control group. The hypothyroid state in mothers during pregnancy was confirmed by measuring total thyroxine [TT[4]] and total triiodothyronine [TT[3]] at gestational day 10. At the end of experiment, the offsprings were sacrificed and free thyroxine [FT[4]] and free triiodothyronine [FT[3]] in sera and neurotransmitters [dopamine, norepinephrine and serotonin] and Na, K-ATPase activity were measured in the cerebral homogenate. Maternal hypothyroidism induced a significant decrease in the cerebral level of dopamine [0.10 +/- 0.01 mg/g vs 1.00 +/- 0.11 mg/g, p<0.001], morepinephrine [0.01 +/- 0.001 mg/g vs 0.53 +/- 0.49 mg/g, p<0.001], serotonin [1.32 +/- 0.12 mg/g vs 1.94 +/- 0.08 mg/g, p<0.001] and Na, K- ATPase activity [3.11 +/- 0.27 umol pi/ mg protein vs 4.90 +/- 0.64 umol pi/mg protein, p< 0.001] as compared with euthyroid group. Treatment with T[3] significantly increased the cerebral level of neurotransmitters [0.53 +/- 0.10, p<0.05, 0.43 +/- 0.19, p<0.05 and 1.77 +/- 0.11, p<0.01 respectively] and Na, K -ATPase activity [3.87 +/- 0.48 umol pi/ mg protein] as compared with the hypothyroid group. T[3] supplementation during the postnatal period through its effect on the cerebral Na, K -ATPase effectively reversed the effect of maternal methimazole-induced hypothyroidism on the cerebral level of dopamine, norepinephrine and serotonin

Spironolactone effects on myocardium changes induced by thyroid hormone in rats / Efeitos da espironolactona sobre as alterações miocárdicas induzidas pelo hormônio tireoideano em ratos

FUNDAMENTO: Estudar o papel do sistema renina-angiotensina-aldosterona na hipertrofia miocárdica induzida pelo hormônio tireoideano, utilizando-se a espironolactona. OBJETIVO: Analisar as alterações morfológicas no miocárdio induzidas pelo hormônio tireoideano e os efeitos da espironolactona nesse processo. MÉTODOS: Foram estudados 40 ratos Wistar, divididos em quatro grupos, que receberam: veículo utilizado para a diluição do hormônio tireoideano (C); levotiroxina sódica (50 µg/rato/dia) (H); espironolactona (0,3 mg/kg/dia) (E) e hormônio tireoideano + espironolactona (HE), nas mesmas doses citadas, durante 28 dias consecutivos. Todos os animais foram submetidos a pesagem, coleta de sangue para dosagens hormonais e realização de ECG no início e no final do experimento. Ao final do período de estudo, os animais foram sacrificados para determinação do peso do ventrículo esquerdo (VE) e obtenção de cortes de VE para análise morfológica. RESULTADOS: Houve aumento dos níveis de T3 no plasma, perda de peso corporal e aumento da freqüência cardíaca nos animais que receberam o hormônio. O peso do VE foi maior nos grupos H e HE. A análise histométrica mostrou maiores diâmetros dos miócitos no grupo H, com os valores decrescentes nos grupos HE, E e C, sendo as diferenças estatisticamente significantes entre todos os grupos. A espironolactona associada ao hormônio tireoideano (HT) diminuiu em 14,6 por cento a hipertrofia transversal dos miócitos. CONCLUSÃO: Em ratos tratados com hormônio tireoideano ocorre hipertrofia cardíaca com aumento do peso do VE e do diâmetro do miócito. A associação de espironolactona ao hormônio tireoideano previne parcialmente essa hipertrofia por mecanismos ainda desconhecidos.

BACKGROUND: To study the possible role of aldosterone on thyroid hormone-induced myocardium hypertrophy, using spironolactone. OBJECTIVE: To evaluate morphological changes in the myocardium induced by thyroid hormone and the possible effects of spironolactone use on these alterations. METHODS: Forty Wistar rats were studied. The animals were allocated to four groups and were given: the vehicle used for dilution of the thyroid hormone (C); sodium levothyroxin at 50 µg/rat/day (H); spironolactone, 0.3 mg/kg/day (S); or thyroid hormone plus spironolactone (HS), at the same doses mentioned above, for 28 consecutive days. All the animals were weighed, had blood drawn for hormonal measurements and underwent ECG at the start and the end of the experiment. At the end of experiment all animals were euthanized, the weight of the left ventricle (LV) was determined and LV slices were obtained for morphological analysis. RESULTS: There was an increase in T3 levels, decrease of body weight and higher heart rate in the animals from group H. The LV weight was significantly higher in the H e HS groups. The histometric analyses that measured the diameter of the myocytes showed higher values in group H and a progressive decrease in groups HS, S and C, with a significant difference among all the groups. The addition of spironolactone decreased the transversal myocyte hypertrophy by 14.6 percent. CONCLUSION: Rats treated with thyroid hormone present cardiac hypertrophy with increased LV weight and greater myocyte diameter. Spironolactone, when associated with thyroid hormone, can partially prevent this hypertrophy through mechanisms that are yet to be determined.

Estudo morfométrico do fígado de ratos submetidos a doses supra fisiológicas de tiroxina / Liver morphological study of rats submitted to supra physiologic doses of thyroxine

Tireotoxicose é o estado hipermatabólico causado pelo excesso de hormônios tireoidianos circulantes, que exercem sua funçäo praticamente em todos os tecidos. No presente estudo avaliou-se, por métodos estereológicos, o fígado de ratos tratados com doses supra fisiológicas de T4 (20µg/10g de peso de corporal) durante 20 dias. Os níveis séricos de T4 desses animais estavam significantemente elevados (p=0,02). Houve tendência a perda de peso corporal dos animais tratados em relaçäo ao grupo controle (p=0,10), enquanto o peso do fígado teve aumento, embora näo significativo (p=0,08). A proporçäo do parênquima lobular foi maior (p=0,05) e a fraçäo volumétrica do parênquima lobular ocupada pelas células de Kupffer foi significantemente menor (p=0,05) nos animais hipertireóideos que nos controles. Houve depleçäo que nos controles. Houve depleçäo significativa do glicogênio hepático na parênquima lobular, em relaçäo ao grupo controle (p=0,008). Concluiu-se, entäo, que a tireotoxicose provoca hiperplasia e/ou hipertrofia dos hepatócitos, com reduçäo das reservas energéticas.