methylthiouracil and Cardiomegaly

Since stimulation of heart hypertrophy by pressure overload was previously shown to be accompanied by a densification of microtubule network in rat heart myocytes, we verified that similar process occurred during postnatal growth in euthyroid rats and in hypothyroid rats whose growth was stimulated by 4 micrograms/day L-thyroxine (T4). For this purpose, tubulin, the constituent protein of microtubules, was immunolabeled in myocytes isolated at various times after birth. Myocyte hypertrophy was evaluated by myocyte size, the number of nuclei per cell and isomyosin expression. In hypothyroid rats, the microtubule network, which was underdeveloped, was most dense around the nucleus. During the phase of fast myocyte hypertrophy observed in euthyroid rats during late postnatal development and in hypothyroid rats after T4 administration, transient microtubule densification occurred in a myocyte subpopulation in which size was mainly determined by the rate of myocyte hypertrophy. The densification process and its kinetics resembled those observed when heart hypertrophy was induced by pressure overload. It is concluded that in rat heart myocytes undergoing hypertrophy, microtubule densification might be related to fast sarcomerogenesis, whether the stimulus is mechanical (e.g., pressure overload) or hormonal (e.g., T4).

Topics: Aging; Animals; Cardiomegaly; Female; Fluorescent Antibody Technique; Heart; Hypothyroidism; In Vitro Techniques; Methylthiouracil; Microtubules; Myocardium; Pregnancy; Rats; Rats, Inbred Strains; Thyroxine

With reference to the indirect evidence showing that heart growth in the presence of a cardiac overload is modulated by the adrenal cortex, we studied heart reactions to overloading (ligation of the abdominal aorta or hyperthyroidism) with simultaneous administration of aminoglutethimide, an inhibitor of steroidogenesis. Aminoglutethimide (Elipten CIBA, 0.5% in the diet) markedly inhibited the growth reaction of the heart 14 days after ligation of the abdominal aorta (reducing the aortal blood flow to about 40%) or after the administration of dried thyroid (Thyreoidin SPOFA, 0.2% in the diet). The effect of aminoglutethimide is evidently not due to its simultaneous antithyroid action, because methylthiouracil (Alkiron SPOFA, 0.2% in the diet) did not limit heart growth after ligation of the abdominal aorta, despite its having a stronger goitrogenic effect than aminoglutethimide. The results are a further contribution to the series of indirect evidence of the modulating effect of the adrenal cortex on heart growth.

Topics: Aminoglutethimide; Animals; Aorta, Abdominal; Cardiomegaly; Heart; Hyperthyroidism; Male; Methylthiouracil; Rats; Rats, Inbred Strains