Direct anabolic effects of thyroid hormone on isolated mouse heart

Crie, J. S.; Wakeland, J. R.; Mayhew, Bobbie; Wildenthal, K.

doi:10.1152/ajpcell.1983.245.5.c328

Cited by 25 publications

(10 citation statements)

References 24 publications

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“…How¬ ever, in this second study, myosin isoenzyme changes did occur in the absence of heart weight changes, suggesting that at least part of the thyroid hormone changes were mediated by a direct action on the heart. This is also supported by a previously reported study in which tri-iodothyronine produced increased protein synthesis in an organ culture model of the isolated mouse heart, in the absence of the usual systemic, metabolic and haemodynamic effects of thyroid hormones (Crie et al 1983). An important difference between all of these studies and the present study is the time-scale over which thy¬ roid dysfunction was induced.…”

Section: Discussionsupporting

confidence: 84%

Endocrine and cardiac paracrine actions of insulin-like growth factor-I (IGF-I) during thyroid dysfunction in the rat: is IGF-I implicated in the mechanism of heart weight/body weight change during abnormal thyroid function?

Thomas¹,

Miell²,

Taylor³

et al. 1993

Journal of Molecular Endocrinology

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Thyroid hormones are essential for the normal growth and development of many tissues. In the rat, hypothyroidism is associated with growth impairment, and hyperthyroidism with the development of a hypercatabolic state and skeletal muscle wasting but, paradoxically, cardiac hypertrophy. The mechanism by which thyroid hormone produces cardiac hypertrophy and myosin isoenzyme changes remains unclear. The role of IGF-I, an anabolic hormone with both paracrine and endocrine actions, in producing cardiac hypertrophy was investigated during this study in hyperthyroid, hypothyroid and control rats. A treated hypothyroid group was also included in order to assess the effect of acute normalization of thyroid function. Body weight was significantly lower in the hyperthyroid (mean +/- S.E.M.; 535.5 +/- 24.9 g, P < 0.05), hypothyroid (245.3 +/- 9.8 g, P < 0.001) and treated hypothyroid (265.3 +/- 9.8 g, P < 0.001) animals when compared with controls (618.5 +/- 28.6 g). Heart weight/body weight ratios were, however, significantly increased in the hyperthyroid (2.74 +/- 0.11 x 10(-3), P < 0.01) and treated hypothyroid (2.87 +/- 0.07 x 10(-3), P < 0.001) animals when compared with controls (2.26 +/- 0.03 x 10(-3). Serum IGF-I concentrations were similar in the control and hyperthyroid rats (0.91 +/- 0.07 vs 0.78 +/- 0.04 U/ml, P = 0.26), but bioactivity was reduced by 70% in hyperthyroid serum, suggesting a circulating inhibitor of IGF. Serum IGF-I levels (0.12 +/- 0.03 U/ml, P < 0.001) and bioactivity (0.12 +/- 0.04 U/ml, P < 0.001) were significantly lower in the hypothyroid group. Liver IGF-I mRNA levels were not statistically different in the control and hyperthyroid animals, but were significantly reduced in the hypothyroid animals (P < 0.05 vs control). Heart IGF-I mRNA levels were similar in the control and hypothyroid rats, but were significantly increased in the hyperthyroid and treated hypothyroid animals (increased by 32% in hyperthyroidism, P < 0.05; increased by 57% in treated hypothyroidism, P < 0.01). Cardiac IGF-I was significantly elevated in hyperthyroidism (0.16 +/- 0.01 U/mg heart tissue, P < 0.01), was low in hypothyroidism (0.08 +/- 0.01 U/mg, P < 0.01) and was normalized in the treated hypothyroid group (0.11 +/- 0.01 U/mg vs control, 0.13 +/- 0.01 U/mg). Low body mass during both hypothyroidism and hyperthyroidism is therefore associated with reduced systemic IGF bioactivity. In hypothyroidism there is a primary defect in the endocrine function of IGF-I, while in hyperthyroidism serum IGF bioactivity is reduced in the presence of normal endocrine production of this anabolic hormone.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionsupporting

confidence: 84%

Endocrine and cardiac paracrine actions of insulin-like growth factor-I (IGF-I) during thyroid dysfunction in the rat: is IGF-I implicated in the mechanism of heart weight/body weight change during abnormal thyroid function?

Thomas¹,

Miell²,

Taylor³

et al. 1993

Journal of Molecular Endocrinology

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show abstract

“…This difference was thought to be secondary to the work overload of the heart in the hyperthyroid rats. However, recent evidence obtained in the in vitro incubated foetal mouse heart, shows direct effects of T3 similar to those obtained in the intact hyperthy¬ roid rat (Crie et al 1983). …”

Section: Discussionsupporting

confidence: 67%

T3 stimulation of 2-deoxy-D-glucose uptake in cultured chick embryo carcass derived cells, requires neosynthesis of proteins

Gordon

Schwartz

Gross

1987

Acta Endocrinologica

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T3 stimulated, in a dose dependent manner, the uptake of 2-deoxy-D-glucose (2-DOG) into cultured chick embryo carcass derived cells. A significant increase in sugar uptake was seen already at a T3 concentration of 1 pmol/l. The stimulation of 2-DOG uptake increased with time during the 6 h of exposure to T3. The hormone also stimulated, within 45 min, the incorporation of [3H]leucine and [3H]uridine into the trichloroacetic acid precipitable material of these cells. Actinomycin-D (100 \g=m\g/l) and cycloheximide (1 mg/l) each were capable of blocking the stimulatory effect of 10\m=-\8mol/l T3 on sugar uptake and on uridine and leucine incorporation. Thus, T3 in these cultured chick embryo cells stimulated sugar transport through processes dependent on neosynthesis of proteins. In this respect the effect of T3 is different from that seen in cultured chick embryo cardiomyocytes. In previous publications (Segal & Gordon 1977a,b; Segal et al. 1977; Dickstein et al. 1983; Gordon et al. 1986), it was shown that T3 stimu¬ lates sugar transport into cultured chick embryo cardiomyocytes. This effect, which occurred with¬ in the first 6 h of exposure to physiological concentrations of the hormone, was not suppres¬ sed by actinomycin-D, cycloheximide or puromycin and could be elicited even when the T3 was presented while covalently bound to erythrocytes (Dickstein et al. 1983). These data suggest that the plasma membrane in cardiomyocytes is a target for a direct action of thyroid hormones. Further investigation into the biochemical events of the plasma membrane that lead to the stimulation of sugar transport is hampered because these cells contract rhythmically.For this reason we looked at the effect of T3 in a quiescent cell culture of chick embryo cells derived from its carcass. The data presented in this work show that T3 stimulates rapidly the uptake of 2-deoxy-D-glucose (2-DOG) into these cells. T3 stimulates equally rapidly the incorpora¬ tion of both [3H]leucine and [3H]uridine into trichloroacetic acid (TCA) precipitable material, and both actinomycin-D and cycloheximide block effectively these stimulations by T3. Therefore these cells differ from cultured cardiomyocytes in that the effect of T3 is mediated most probablythrough its effect on protein synthesis. Materials and MethodsMedium

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“…With mouse hearts in organ culture, T3 increased the rate of protein synthesis, although no changes in contractility were observed. 92 In cultured fetal cat cardiomyocytes, thyroid hormone caused a shift in the content of myosin isozyme from V3 to V1,93 an accumulation of a-myosin heavychain mRNA, and inhibition of expression of /3-myosin heavy-chain mRNA.94 In cultured chick cardiomyocytes, the addition of T3 increased the fractional rates of protein synthesis and cell growth by 10-16% and 20-40%, respectively.95 These studies demonstrate that thyroid hormone directly controls gene expression and cellular growth in cardiac myocytes. In unpublished studies by P.J.…”

Section: Endocrine Control Of Cardiac Hypertrophy Thyroid Hormonementioning

confidence: 99%