The influence of thyroid hormones on the growth of the atria and ventricles of the heart in immature rats

Abstract

The normal plasma concentrations of tri-iodothyronine (T3) and thyroxine (T4) increase approximately six- and fourfold respectively between the end of gestation and weaning in the rat. This early postnatal surge of thyroid hormones was experimentally modified to produce either a state of hypo- or hyperthyroidism. The growth and rates of protein turnover in the atria and ventricles of the heart were studied, 12 and 20 days postpartum, both as a function of age and of changing thyroid status. Neonatal hypothyroidism was induced by adding propylthiouracil to the mothers' drinking water late in gestation and throughout lactation. Hyperthyroidism was achieved by giving the suckling pups daily injections of T4 from day 3 postpartum onwards. Between 12 and 20 days the weight and protein mass of the combined ventricles of the euthyroid animals approximately doubled, along with substantial increases (50%) in the RNA and DNA contents. Over this same 8 days, growth in the combined atria was much slower. During the same period, hypothyroidism significantly retarded the growth of these immature rats and their atria and ventricles. Both the rates of protein synthesis and protein degradation were decreased in the atria and ventricles. In contrast, hyperthyroidism significantly increased growth in both types of cardiac tissue, this being more pronounced in the atria than in the ventricles between 12 and 20 days. The rates of protein synthesis were increased accordingly, principally by increases in the ribosomal activities. In conclusion, thyroid hormones clearly influence the early postnatal growth of the atria and ventricles of the heart in the rat.

Adeno-Associated Virus-Mediated Expression of Thyroid Hormone Receptor Isoforms-α1 and -β1 Improves Contractile Function in Pressure Overload-Induced Cardiac Hypertrophy

“…These observations, along with other phenotypic changes such as an increased reliance on glucose for energy metabolism (6), suggest that the hypertrophied heart reverts to a more fetal-like state. Normally, maturation of the heart with respect to MHC and SERCA expression coincides with an increase in plasma levels of thyroid hormone shortly after birth (7,8).Recent studies have shown hypertrophy and heart failure to be associated with a decrease in circulating thyroid hormone or the development of sick thyroid syndrome (3,9). In addition, heart failure itself has been shown to be associated with a reduction in the actual number of thyroid hormone receptors in the cardiac myocyte (10-13), suggesting that even though the level of thyroid hormone may not change, the heart itself may be less responsive to signaling by thyroid hormone.…”

“…These observations, along with other phenotypic changes such as an increased reliance on glucose for energy metabolism (6), suggest that the hypertrophied heart reverts to a more fetal-like state. Normally, maturation of the heart with respect to MHC and SERCA expression coincides with an increase in plasma levels of thyroid hormone shortly after birth (7,8).…”

Thyroid‐induced changes in the growth of the Liver, Kidney, and Diaphragm of Neonatal Rats

“…This presumably suggests a high level of tolerance in the rat, compared with other species andior a fundamental difference between the responsiveness of neonatal and adult animals. The latter seems unlikely since cardiac hypertrophy is expressed in response to hyperthyroidism, regardless of age (Feldman et al, 1986;Canavan et al, 1994).…”

“…However, subsequent increases in these hormone levels appear to provoke different reactions within the different tissues. Tissues with very high rates of protein synthesis, e.g., the liver (Table 3) and lung (Holt et al, 19931, are relatively unresponsive to excess thyroid hormones, but those with low absolute rates of synthesis, e.g., the striated muscles, are the most responsive (Table 3; Canavan et al, 1994). The tissue specific nature of the induced changes in protein turnover do not appear to relate to the type of thyroid hormone receptors that are expressed.…”

Uptake of tri-iodothyronine and thyroxine in myoblasts and myotubes of the embryonic heart cell line H9c2(2-1)

“…In both humans and rodents, the start of fetal thyroid activity is associated with a rise in cardiac contractility (Cluzeaut & Maurer-Schultze 1986, Mayhew et al 1997. Canavan et al (1994) showed that hypothyroidism significantly delayed this development of the heart, while hyperthyroidism led to the opposite result.…”