scholarly journals Thyroid hormone signaling and consequences for cardiac development

2019 ◽  
Vol 242 (1) ◽  
pp. T145-T160 ◽  
Author(s):  
Natasha N Chattergoon
Keyword(s):  
Thyroid Hormone ◽  
Cardiovascular Health ◽  
Neuronal Development ◽  
Cardiac Development ◽  
Perinatal Period ◽  
Organ Systems ◽  
Fetal Cardiomyocytes ◽  
Maturation Stages ◽  
Fetal Size ◽  
Near Term

The fetal heart undergoes its own growth and maturation stages all while supplying blood and nutrients to the growing fetus and its organs. Immature contractile cardiomyocytes proliferate to rapidly increase and establish cardiomyocyte endowment in the perinatal period. Maturational changes in cellular maturation, size and biochemical capabilities occur, and require, a changing hormonal environment as the fetus prepares itself for the transition to extrauterine life. Thyroid hormone has long been known to be important for neuronal development, but also for fetal size and survival. Fetal circulating 3,5,3′-triiodothyronine (T3) levels surge near term in mammals and are responsible for maturation of several organ systems, including the heart. Growth factors like insulin-like growth factor-1 stimulate proliferation of fetal cardiomyocytes, while thyroid hormone has been shown to inhibit proliferation and drive maturation of the cells. Several cell signaling pathways appear to be involved in this complicated and coordinated process. The aim of this review was to discuss the foundational studies of thyroid hormone physiology and the mechanisms responsible for its actions as we speculate on potential fetal programming effects for cardiovascular health.

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

2014 ◽  
Vol 307 (8) ◽  
pp. H1216-H1225 ◽  
Author(s):  
N. N. Chattergoon ◽  
S. Louey ◽  
P. J. Stork ◽  
G. D. Giraud ◽  
K. L. Thornburg
Keyword(s):  
Cell Cycle ◽  
Intracellular Signaling ◽  
Cardiac Development ◽  
Hormonal Control ◽  
Binucleated Cells ◽  
Age Related ◽  
Fetal Cardiomyocytes ◽  
Near Term ◽  
In Cells

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 p70S6K 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 p70S6K 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.

scholarly journals Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse

1990 ◽  
Vol 271 (2) ◽  
pp. 373-379 ◽  
Author(s):  
R Vranckx ◽  
L Savu ◽  
M Maya ◽  
E A Nunez
Keyword(s):  
Thyroid Hormone ◽  
Serum Proteins ◽  
Perinatal Period ◽  
Binding Activity ◽  
Scatchard Analysis ◽  
Postnatal Life ◽  
High Association ◽  
Thyroxine Binding Globulin ◽  
Major Development ◽  
Maturation Stages

We confirm our finding of a major development-regulated thyroxine-binding globulin (TBG) in the serum of the euthyroid mouse and investigate a number of its binding, structural and regulatory properties. Between 16 days foetal and 60 days postnatal life, the thyroxine (T4)- and tri-iodothyronine (T3)-binding activities of the sera show a striking ontogenic pattern: the binding is 2-3 times higher in foetuses than in mothers, then further increases after birth, reaching between 3 and 5 days maximum values which are 7-8 times higher than the adult ones. This pattern is not correlated with the ontogenesis of the acknowledged specific (transthyretin, TTR) and non-specific (albumin, alpha 1-foetoprotein) thyroid-hormone carriers of the mouse sera. PAGE studies demonstrate that the protein responsible for the elevated binding of the perinatal period is an alpha 1-globulin, with a migration similar to that of human and rat TBGs. Scatchard analysis is consistent with the notions that the T4-binding sites of TBG have high association constants, about two orders of magnitude above the T4 sites of TTR (10(9) M-1 as against 10(7) M-1) and low capacities (37 and 4 nmol/g of serum proteins in pups and adults respectively). Isoelectric focusing (i.e.f.) demonstrates that mouse TBG is a microheterogeneous protein separable, as a function of the pH gradient, in up to 10-12 isoforms, Marked shifts of the relative abundance of isoforms in the course of development are evidenced. The modulation of the TBG binding activity by non-esterified fatty acids (NEFA) and the control of its synthesis by the thyroid status are also reported. Mono- and poly-unsaturated NEFAs are strong inhibitors of the TBG, although they affect TTR less readily. On the other hand, the biosynthesis and/or secretion of TBG, but not of TTR, is under thyroid-hormone control, experimental hypothyroidism inducing a marked increase of the serum TBG. The TBG of mouse behaves as a highly significant parameter of development, pointing to a likely important function of the protein in the process of maturation. Our finding of major TBGs in both euthyroid rats and mice suggests that TBG is more widely spread than was thought until now, but difficult to detect in certain species outside definite maturation stages.

scholarly journals Thyroid hormone insufficiency alters the expression of psychiatric disorder-related molecules in the hypothyroid mouse brain during the early postnatal period

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katsuya Uchida ◽  
Kentaro Hasuoka ◽  
Toshimitsu Fuse ◽  
Kenichi Kobayashi ◽  
Takahiro Moriya ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Critical Period ◽  
Neuronal Development ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Early Postnatal Period ◽  
Cortical Layers ◽  
Neuronal Nuclei ◽  
Antithyroid Agents

AbstractThe functional role of thyroid hormone (TH) in the cortex and hippocampus of mouse during neuronal development was investigated in this study. TH insufficiency showed a decrease in the expression of parvalbumin (PV) in the cortex and hippocampus of pups at postnatal day (PD) 14, while treatment with thyroxine from PD 0 to PD 14 ameliorated the PV loss. On the other hand, treatment with antithyroid agents in adulthood did not result in a decrease in the expression of PV in these areas. These results indicate the existence of a critical period of TH action during the early postnatal period. A decrease in MeCP2-positive neuronal nuclei was also observed in the cortical layers II–IV of the cerebral cortex. The brains were then stained with CUX1, a marker for cortical layers II–IV. In comparison with normal mice, CUX1 signals were decreased in the somatosensory cortex of the hypothyroid mice, and the total thickness of cortical layers II–IV of the mice was lower than that of normal mice. These results suggest that TH insufficiency during the perinatal period strongly and broadly affects neuronal development.

Newborn Screening for Congenital Hypothyroidism: Recommended Guidelines

PEDIATRICS ◽  
1993 ◽  
Vol 91 (6) ◽  
pp. 1203-1209
Author(s):  
Keyword(s):  
Thyroid Hormone ◽  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Placental Transfer ◽  
Fetal Brain ◽  
Iodothyronine Deiodinase ◽  
Screening Programs ◽  
Organ Systems ◽  
Fetal Hypothyroidism ◽  
Maternal Thyroid

Congenital hypothyroidism (CH) represents one of the most common preventable causes of mental retardation. The fetal hypothalamic-pituitary-thyroid axis begins to function by midgestation and is mature in the term infant at delivery. If fetal hypothyroidism develops, untoward effects may be demonstrated in certain organ systems, including the central nervous system and skeleton. However, most infants with CH appear normal at birth. Recent data suggest that the hypothyroid fetus is protected to a certain extent by placental transfer of maternal thyroid hormone; serum thyroxine (T4) levels in the cord blood of athyroid fetuses approximate one third of maternal levels.1 In addition, studies in animal models of hypothyroidism demonstrate increased levels of brain iodothyronine deiodinase, the enzyme which converts T4 to triiodothyronine (T3). In the hypothyroid fetus, this increased enzyme acting on T4 of maternal origin is sufficient to produce near normal fetal brain T3 concentrations.2 Thus, it appears that early detection and treatment of congenital hypothyroidism should have the potential to completely reverse the effects of fetal hypothyroidism in all but the most severe cases, for example, athyreotic infants born to mothers with thyroid problems resulting in inadequate placental transfer of maternal thyroid hormone. Since the development of pilot screening programs for CH in Quebec and Pittsburgh in 1974,3 newborn screening for CH has become routine in essentially all developed countries of the world and is under development in Eastern Europe, South America, Asia, and Africa. In North America it is estimated that more than 5 million newborns are screened, with approximately 1400 infants with congenital hypothyroidism detected annually.

scholarly journals 335 CARDIAC DEVELOPMENT IN THE PERINATAL PERIOD

1985 ◽  
Vol 19 (4) ◽  
pp. 166A-166A
Author(s):  
Victor Whitman ◽  
H Gregg Schuler ◽  
Raymond R Fripp
Keyword(s):  
Cardiac Development ◽  
Perinatal Period

The role of non-coding RNA/microRNAs in cardiac disease

2018 ◽  
Author(s):  
Yolan J. Reckman ◽  
Yigal M. Pinto
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Cardiac Disease ◽  
Cardiac Development ◽  
Rna Transcripts ◽  
The Past ◽  
Non Coding Rna ◽  
Organ Systems ◽  
Non Coding Rnas

In the past two decades, our knowledge about non-coding DNA has increased tremendously. While non-coding DNA was initially discarded as ‘junk DNA’, we are now aware of the important and often crucial roles of RNA transcripts that do not translate into protein. Non-coding RNAs (ncRNAs) play important functions in normal cellular homeostasis and also in many diseases across all organ systems. Among the different ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been studied the most. In this chapter we discuss the role of miRNAs and lncRNAs in cardiac disease. We present examples of miRNAs with fundamental roles in cardiac development (miR-1), hypertrophy (myomiRs, miR-199, miR-1/133), fibrosis (miR-29, miR-21), myocardial infarction (miR-15, miR17~92), and arrhythmias/conduction (miR-1). We provide examples of lncRNAs related to cardiac hypertrophy (MHRT, CHRF), myocardial infarction (ANRIL, MIAT), and arrhythmias (KCNQ1OT1). We also discuss miRNAs and lncRNAs as potential therapeutic targets or biomarkers in cardiac disease.

scholarly journals Thyroid Hormone Deficiency Suppresses Fetal Pituitary–Adrenal Function Near Term: Implications for the Control of Fetal Maturation and Parturition

Thyroid ◽  
2020 ◽  
Author(s):  
Emily J. Camm ◽  
Isabella Inzani ◽  
Miles J. De Blasio ◽  
Katie L. Davies ◽  
India R. Lloyd ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Adrenal Function ◽  
Hormone Deficiency ◽  
Near Term

Platelet-activating factor modulates pulmonary vasomotor tone in the perinatal lamb

1998 ◽  
Vol 85 (3) ◽  
pp. 1079-1085 ◽  
Author(s):  
Basil O. Ibe ◽  
Sue Hibler ◽  
J. Usha Raj
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Platelet Activating Factor ◽  
Perinatal Period ◽  
Arterial Blood Flow ◽  
Vasomotor Tone ◽  
Arterial Blood ◽  
Determine Role ◽  
Pulmonary Arterial ◽  
Near Term

Eight near-term fetal lambs were studied acutely in utero to determine role of platelet-activating factor (PAF) in the regulation of vasomotor tone in systemic and pulmonary circulations in the immediate perinatal period. Four fetal lambs were studied predelivery and 2 h postdelivery to determine circulating PAF levels. Aortic and pulmonary arterial pressures and cardiac output were measured continuously, and systemic and pulmonary vascular resistances were calculated. Left pulmonary arterial blood flow was also measured in four fetal lambs. After delivery and oxygenation, circulating PAF levels fell significantly. When WEB-2170, a specific PAF-receptor antagonist, was infused to block effect of endogenous PAF in the eight near-term fetal lambs, systemic vascular resistance fell 30% but pulmonary vascular resistance fell dramatically by 68%. Specificity of WEB-2170 was tested in juvenile lambs and was found to be very specific in lowering vasomotor tone only when tone was elevated by action of PAF. Our data show that endogenous PAF levels in the fetus contribute to maintain a high basal systemic and pulmonary vasomotor tone and that a normal fall in circulating PAF levels after birth and oxygenation may facilitate fall in pulmonary vascular resistance at birth.

scholarly journals Air pollution and cardiovascular disease: car sick

2019 ◽  
Author(s):  
Mark R Miller ◽  
David E Newby
Keyword(s):  
Air Pollution ◽  
Diesel Exhaust ◽  
Ultrafine Particles ◽  
Cardiovascular Health ◽  
Cardiovascular Effects ◽  
Urban Environments ◽  
Vehicle Exhaust ◽  
Diesel Exhaust Exposure ◽  
Particle Matter ◽  
Organ Systems

Abstract The cardiovascular effects of inhaled particle matter (PM) are responsible for a substantial morbidity and mortality attributed to air pollution. Ultrafine particles, like those in diesel exhaust emissions, are a major source of nanoparticles in urban environments, and it is these particles that have the capacity to induce the most significant health effects. Research has shown that diesel exhaust exposure can have many detrimental effects on the cardiovascular system both acutely and chronically. This review provides an overview of the cardiovascular effects on PM in air pollution, with an emphasis on ultrafine particles in vehicle exhaust. We consider the biological mechanisms underlying these cardiovascular effects of PM and postulate that cardiovascular dysfunction may be implicated in the effects of PM in other organ systems. The employment of multiple strategies to tackle air pollution, and especially ultrafine particles from vehicles, is likely to be accompanied by improvements in cardiovascular health.

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