Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro

Chattergoon, Natasha N.; Giraud, G; Thornburg, Kent L.

doi:10.1677/joe-06-0114

Cited by 55 publications

(76 citation statements)

References 43 publications

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“…They promote a switch from proliferation to hypertrophy and differentiation of the cardiomyocytes both at term and earlier in gestation (Chattergoon et al 2012a,b). In a series of in vivo and in vitro studies in fetal sheep, T 3 has been shown to increase the cardiomyocyte size and the population of terminally differentiated binucleated cells in association with downregulation of cell cycle promoters by 50% or more and upregulation of cell cycle suppressors and various molecular mechanisms of cell growth by up to 500% (Chattergoon et al 2007(Chattergoon et al , 2012a. Conversely, thyroidectomy of the sheep fetus reduces the number of binucleate cardiomyocytes by 27% and the relative weight of the heart by 10-15% near term (Chattergoon et al 2012a, Segar et al 2013.…”

Section: The Heart and Cardiovascular Functionmentioning

confidence: 99%

Thyroid hormones in fetal growth and prepartum maturation

Forhead

Fowden

2014

Journal of Endocrinology

342

270

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The thyroid hormones, thyroxine (T 4 ) and triiodothyronine (T 3 ), are essential for normal growth and development of the fetus. Their bioavailability in utero depends on development of the fetal hypothalamic-pituitary-thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T 4 and T 3 concentrations are also affected by gestational age, nutritional and endocrine conditions in utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating the prepartum maturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T 4 and T 3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

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Section: The Heart and Cardiovascular Functionmentioning

confidence: 99%

Thyroid hormones in fetal growth and prepartum maturation

Forhead

Fowden

2014

Journal of Endocrinology

342

270

View full text Add to dashboard Cite

show abstract

“…Both TH-mediated up-and down-regulation of cyclins have been demonstrated in several tissues (Ledda-Columbano et al 2005, Chattergoon et al 2007, Verga Falzacappa et al 2012. TH-mediated regulation of cyclin-CDK complexes leading to cell arrest (Toms et al 1998) or cell differentiation (Ballock et al 2000) has also been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Thyroid status modulates T lymphoma growth via cell cycle regulatory proteins and angiogenesis

Sterle¹,

Valli²,

Cayrol³

et al. 2014

Journal of Endocrinology

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We have shown in vitro that thyroid hormones (THs) regulate the balance between proliferation and apoptosis of T lymphoma cells. The effects of THs on tumor development have been studied, but the results are still controversial. Herein, we show the modulatory action of thyroid status on the in vivo growth of T lymphoma cells. For this purpose, euthyroid, hypothyroid, and hyperthyroid mice received inoculations of EL4 cells to allow the development of solid tumors. Tumors in the hyperthyroid animals exhibited a higher growth rate, as evidenced by the early appearance of palpable solid tumors and the increased tumor volume. These results are consistent with the rate of cell division determined by staining tumor cells with carboxyfluorescein succinimidyl ester. Additionally, hyperthyroid mice exhibited reduced survival. Hypothyroid mice did not differ significantly from the euthyroid controls with respect to these parameters. Additionally, only tumors from hyperthyroid animals had increased expression levels of proliferating cell nuclear antigen and active caspase 3. Differential expression of cell cycle regulatory proteins was also observed. The levels of cyclins D1 and D3 were augmented in the tumors of the hyperthyroid animals, whereas the cell cycle inhibitors p16/INK4A (CDKN2A) and p27/Kip1 (CDKN1B) and the tumor suppressor p53 (TRP53) were increased in hypothyroid mice. Intratumoral and peritumoral vasculogenesis was increased only in hyperthyroid mice. Therefore, we propose that the thyroid status modulates the in vivo growth of EL4 T lymphoma through the regulation of cyclin, cyclin-dependent kinase inhibitor, and tumor suppressor gene expression, as well as the stimulation of angiogenesis.

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“…We previously reported that physiological concentrations of T 3 are powerful suppressants of serum-stimulated proliferation among isolated cardiomyocytes from mid-and late-gestation (7,8). The inhibitory effect is associated with increases in the cell cycle suppressant protein, p21, and decreased expression of the cell cycle protein, cyclin D1.…”

mentioning

confidence: 97%

“…Among the many regulators, insulin-like growth factor 1 (IGF-1) (44) powerfully stimulates proliferation rates of ovine cardiomyocytes and is the most powerful factor in promoting robust growth in the heart. In opposition to IGF-1, thyroid hormone is a powerful antiproliferation hormone that becomes increasingly effective as gestation proceeds (7). Thus the balanced actions of these two hormones determine the cardiomyocyte endowment at birth.…”

mentioning

confidence: 99%

Unexpected maturation of PI3K and MAPK-ERK signaling in fetal ovine cardiomyocytes

Chattergoon

Louey

Stork

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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In the first two-thirds of gestation, ovine fetal cardiomyocytes undergo mitosis to increase cardiac mass and accommodate fetal growth. Thereafter, some myocytes continue to proliferate while others mature and terminally differentiate into binucleated cells. At term (145 days gestational age; dGA) about 60% of cardiomyocytes become binucleated and exit the cell cycle under hormonal control. Rising thyroid hormone (T3) levels near term (135 dGA) inhibit proliferation and stimulate maturation. However, the degree to which intracellular signaling patterns change with age in response to T3 is unknown. We hypothesized that in vitro activation of ERK, Akt, and p70(S6K) by two regulators of cardiomyocyte cell cycle activity, T3 and insulin like growth factor-1 (IGF-1), would be similar in cardiomyocytes at gestational ages 100 and 135 dGA. IGF-1 and T3 each independently stimulated phosphorylation of ERK, Akt, and p70(S6K) in cells at both ages. In the younger mononucleated myocytes, the phosphorylation of ERK and Akt was reduced in the presence of IGF-1 and T3. However, the same hormone combination led to a dramatic twofold increase in the phosphorylation of these signaling proteins in the 135 dGA cardiomyocytes-even in cells that were not proliferating. In the older cells, both mono- and binucleated cells were affected. In conclusion, fetal ovine cardiomyocytes undergo profound maturation-related changes in signaling in response to T3 and IGF-1, but not to either factor alone. Differences in age-related response are likely to be related to milestones in fetal cardiac development as the myocardium prepares for ex utero life.

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Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro

Cited by 55 publications

References 43 publications

Thyroid hormones in fetal growth and prepartum maturation

Thyroid hormones in fetal growth and prepartum maturation

Thyroid status modulates T lymphoma growth via cell cycle regulatory proteins and angiogenesis

Unexpected maturation of PI3K and MAPK-ERK signaling in fetal ovine cardiomyocytes

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