Thyroid hormones and brain development

1995 ◽  
Vol 133 (4) ◽  
pp. 390-398 ◽  
Author(s):  
Juan Bernal ◽  
Jacques Nunez
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Brain Development ◽  
Neuronal Differentiation ◽  
Cell Biology ◽  
Physiological Role ◽  
Hormone Deficiency ◽  
Mammalian Brain

Bernal J, Nunez J. Thyroid hormones and brain development. Eur J Endocrinol 1995;133:390–8. ISSN 0804–4643 Thyroid hormone is a major physiological regulator of mammalian brain development. Cell differentiation, migration and gene expression are altered as a consequence of thyroid hormone deficiency or excess. The physiological role of thyroid hormone can perhaps be defined so as to ensure the timed coordination of different developmental events through specific effects on the rate of cell differentiation and gene expression. All triiodothyronine (T3) receptor isoforms are expressed in the brain and their spatial and temporal patterns of expression suggest unique and complementary functions for the different isoforms. Cell biology studies suggest a role for T3 and its receptors in oligodendroglial and neuronal differentiation and the control of cell death. Some of the effects on neuronal differentiation might be due to an action of thyroid hormone on the production of neurotropins and their receptors. In recent years a number of T3-dependent genes have been identified in the rat brain, such as myelin protein-encoding genes or specific neuronal genes, and thyroid hormone-responsive elements have been demonstrated in some of these genes. The identification of the gene network regulated by thyroid hormone during brain development, the elucidation of the mechanism of regulation and the clarification of the physiological roles of the regulated genes remain major goals for future studies. Jacques Nunez, INSERM U282. Hôpital Henri Mondor, 94010 Créteil, France

scholarly journals Involvement of Thyroid Hormones in Brain Development and Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2693
Author(s):  
Gabriella Schiera ◽  
Carlo Maria Di Liegro ◽  
Italia Di Liegro
Keyword(s):  
Nervous System ◽  
Thyroid Hormones ◽  
Brain Development ◽  
Placental Transfer ◽  
Regulation Of Gene Expression ◽  
Mammalian Brain ◽  
Cancer Proliferation ◽  
Fetal Thyroid ◽  
Genomic Effects ◽  
And Function

The development and maturation of the mammalian brain are regulated by thyroid hormones (THs). Both hypothyroidism and hyperthyroidism cause serious anomalies in the organization and function of the nervous system. Most importantly, brain development is sensitive to TH supply well before the onset of the fetal thyroid function, and thus depends on the trans-placental transfer of maternal THs during pregnancy. Although the mechanism of action of THs mainly involves direct regulation of gene expression (genomic effects), mediated by nuclear receptors (THRs), it is now clear that THs can elicit cell responses also by binding to plasma membrane sites (non-genomic effects). Genomic and non-genomic effects of THs cooperate in modeling chromatin organization and function, thus controlling proliferation, maturation, and metabolism of the nervous system. However, the complex interplay of THs with their targets has also been suggested to impact cancer proliferation as well as metastatic processes. Herein, after discussing the general mechanisms of action of THs and their physiological effects on the nervous system, we will summarize a collection of data showing that thyroid hormone levels might influence cancer proliferation and invasion.

scholarly journals Thyroid Gene Mutations in Pregnant and Breastfeeding Women Diagnosed With Transient Congenital Hypothyroidism: Implications for the Offspring’s Health

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria C. Opazo ◽  
Juan Carlos Rivera ◽  
Pablo A. Gonzalez ◽  
Susan M. Bueno ◽  
Alexis M. Kalergis ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Congenital Hypothyroidism ◽  
Gene Mutations ◽  
Genetic Variations ◽  
Hormone Deficiency ◽  
Iodide Transport ◽  
Transport Defect ◽  
Pregnancy And Lactation ◽  
Transient Congenital Hypothyroidism

Fetus and infants require appropriate thyroid hormone levels and iodine during pregnancy and lactation. Nature endorses the mother to supply thyroid hormones to the fetus and iodine to the lactating infant. Genetic variations on thyroid proteins that cause dyshormonogenic congenital hypothyroidism could in pregnant and breastfeeding women impair the delivery of thyroid hormones and iodine to the offspring. The review discusses maternal genetic variations in thyroid proteins that, in the context of pregnancy and/or breastfeeding, could trigger thyroid hormone deficiency or iodide transport defect that will affect the proper development of the offspring.

scholarly journals Thyroid Hormone Insufficiency during Brain Development Reduces Parvalbumin Immunoreactivity and Inhibitory Function in the Hippocampus

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 92-102 ◽  
Author(s):  
M. E. Gilbert ◽  
L. Sui ◽  
M. J. Walker ◽  
W. Anderson ◽  
S. Thomas ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Brain Development ◽  
Dentate Gyrus ◽  
Perforant Path ◽  
High Dose ◽  
Synaptic Inhibition ◽  
Inhibitory Function ◽  
Inhibitory Circuitry ◽  
Dose Dependent

Thyroid hormones are necessary for brain development. γ-Amino-butyric acid (GABA)ergic interneurons comprise the bulk of local inhibitory circuitry in brain, many of which contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe postnatal hypothyroidism reduces PV immunoreactivity (IR) in rat neocortex. We examined PV-IR and GABA-mediated synaptic inhibition in the hippocampus of rats deprived of thyroid hormone from gestational d 6 until weaning on postnatal d 30. Pregnant dams were exposed to propylthiouracil (0, 3, 10 ppm) via the drinking water, which decreased maternal serum T4 by approximately 50–75% and increased TSH. At weaning, T4 was reduced by approximately 70% in offspring in the low-dose group and fell below detectable levels in high-dose animals. PV-IR was diminished in the hippocampus and neocortex of offspring killed on postnatal d 21, an effect that could be reversed by postnatal administration of T4. Dose-dependent decreases in the density of PV-IR neurons were observed in neocortex and hippocampus, with the dentate gyrus showing the most severe reductions (50–75% below control counts). Altered staining persisted to adulthood despite the return of thyroid hormones to control levels. Developmental cross-fostering and adult-onset deprivation studies revealed that early postnatal hormone insufficiency was required for an alteration in PV-IR. Synaptic inhibition of the perforant path-dentate gyrus synapse evaluated in adult offspring, in vivo, revealed dose-dependent reductions in paired pulse depression indicative of a suppression of GABA-mediated inhibition. These data demonstrate that moderate degrees of thyroid hormone insufficiency during the early postnatal period permanently alters interneuron expression of PV and compromises inhibitory function in the hippocampus.

Hypothyroidism does not affect the dihydropyridine sensitivity of precontracted murine uterus

2003 ◽  
Vol 81 (9) ◽  
pp. 890-893 ◽  
Author(s):  
Jörg W Wegener ◽  
Matthias Lee ◽  
Franz Hofmann
Keyword(s):  
Smooth Muscle ◽  
Cell Differentiation ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Rat Uterus ◽  
Hormone Levels ◽  
Uterine Muscle ◽  
Channel Expression ◽  
Thyroid Hormone Levels ◽  
Pregnant State

Thyroid hormones are known to influence various processes of cell differentiation. Recently, it was reported that hypothyroidism reduces the sensitivity to Ca2+-channel antagonists in the rat uterus. We examined the sensitivity to dihydropyridines of the uterus from mice that had reduced thyroid hormone levels. Isradipine relaxed with the same potency precontracted uterine muscle strips from control and hypothyroid mice, independently from a pseudo-pregnant state. These results demonstrate that hypothyroidism does not change dihydropyridine sensitivity (i.e., the pattern of Ca2+-channel expression) in the murine uterus.Key words: uterus, smooth muscle, Ca2+ channel, isradipine.

Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

2010 ◽  
Vol 397 (3) ◽  
pp. 548-552 ◽  
Author(s):  
Rohit Anthony Sinha ◽  
Amrita Pathak ◽  
Vishwa Mohan ◽  
Satish Babu ◽  
Amit Pal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Brain Development ◽  
Rat Brain ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression

Neonatal hyperthyroidism alters submandibular gland epidermal growth factor response to thyroxine in the adult mouse

1985 ◽  
Vol 63 (9) ◽  
pp. 1151-1154
Author(s):  
Peter Walker
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Thyroid Hormone ◽  
Epidermal Growth Factor ◽  
Thyroid Hormones ◽  
Submandibular Gland ◽  
Adult Mice ◽  
Neonatal Hyperthyroidism ◽  
Epidermal Growth ◽  
And Control

Neonatal hyperthyroidism (NH) in the rat is associated with permanent reductions in serum thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations in the adult, changes suggestive of a hypothyroid state. In the adult NH rat, the thyrotroph appears to be more sensitive to the feedback effects of thyroid hormones. To determine whether thyroid hormone sensitive tissues retain their responsiveness to thyroid hormones, the long-term effects of NH on mouse submandibular gland (SMG) epidermal growth factor (EGF) content were examined. NH was induced in female mice by 20 daily subcultaneous injections of 0.4 μg of T4 per gram of body weight. Control female mice received daily injections of vehicle alone. At 21 days of age, NH and control mice were sacrificed and SMG EGF content was measured by specific radioimmunoassay. SMG EGF content and concentration in 21-day-old NH mice exceeded that of control mice by 2400- and 1500-fold, respectively (P < 0.001). SMG EGF content and concentration in adult (90-day-old) NH mice were slightly, but not significantly, lower than those of control mice. Mean SMG weight, however, was significantly decreased in adult NH mice (P < 0.01). Interestingly, SMG content and concentration of EGF in adult NH mice were lower than in 21-day-old NH mice. After 5 days T4 treatment (16 μg/d) of adult mice, SMG weight in NH mice increased significantly (P < 0.01) but was unchanged in control mice. SMG EGF content and concentration increased significantly in both adult NH and control mice (P < 0.01). However, the magnitude of the increase was markedly obtunded in adult NH mice. These observations indicate that thyroid hormones precociously and exponentially increase SMG EGF content and concentration in neonatal mice. The marked increases strongly suggest thyroid hormone mediated synthesis of EGF and acceleration of maturation of gene expression for EGF synthesis. In addition, NH appears to modify thyroid hormone regulation of gene expression for EGF synthesis in adult mice.

scholarly journals Hematopoiesis in aged female mice devoid of thyroid hormone receptors

2020 ◽  
Vol 244 (1) ◽  
pp. 83-94 ◽  
Author(s):  
Ángela Sánchez ◽  
Constanza Contreras-Jurado ◽  
Diego Rodríguez ◽  
Javier Regadera ◽  
Susana Alemany ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
B Cell ◽  
Knockout Mice ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Dominant Negative ◽  
Thyroid Hormone Receptors ◽  
Female Mice

Hypothyroidism is often associated with anemia and immunological disorders. Similar defects are found in patients and in mice with a mutated dominant-negative thyroid hormone receptor α (TRα) and in knockout mice devoid of this receptor, suggesting that this isoform is responsible for the effects of the thyroid hormones in hematopoiesis. However, the hematological phenotype of mice lacking also TRβ has not yet been examined. We show here that TRα1/TRβ-knockout female mice, lacking all known thyroid hormone receptors with capacity to bind thyroid hormones, do not have overt anemia and in contrast with hypothyroid mice do not present reduced Gata1 or Hif1 gene expression. Similar to that found in hypothyroidism or TRα deficiency during the juvenile period, the B-cell population is reduced in the spleen and bone marrow of ageing TRα1/TRβ-knockout mice, suggesting that TRβ does not play a major role in B-cell development. However, splenic hypotrophy is more marked in hypothyroid mice than in TRα1/TRβ-knockout mice and the splenic population of T-lymphocytes is not significantly impaired in these mice in contrast with the reduction found in hypothyroidism. Our results show that the overall hematopoietic phenotype of the TRα1/TRβ-knockout mice is milder than that found in the absence of hormone. Although other mechanism/s cannot be ruled out, our results suggest that the unoccupied TRs could have a negative effect on hematopoiesis, likely secondary to repression of hematopoietic gene expression.

scholarly journals Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Eleonore Fröhlich ◽  
Richard Wahl
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Virus Disease ◽  
Physiological Role ◽  
Promising Candidate ◽  
Reverse T3 ◽  
Metabolic Dysregulation ◽  
Main Effects ◽  
Potential Use

Thyroxine and triiodothyronine (T3) are classical thyroid hormones and with relatively well-understood actions. In contrast, the physiological role of thyroid hormone metabolites, also circulating in the blood, is less well characterized. These molecules, namely, reverse triiodothyronine, 3,5-diiodothyronine, 3-iodothyronamine, tetraiodoacetic acid and triiodoacetic acid, mediate both agonistic (thyromimetic) and antagonistic actions additional to the effects of the classical thyroid hormones. Here, we provide an overview of the main factors influencing thyroid hormone action, and then go on to describe the main effects of the metabolites and their potential use in medicine. One section addresses thyroid hormone levels in corona virus disease 19 (COVID-19). It appears that i) the more potently-acting molecules T3 and triiodoacetic acid have shorter half-lives than the less potent antagonists 3-iodothyronamine and tetraiodoacetic acid; ii) reverse T3 and 3,5-diiodothyronine may serve as indicators for metabolic dysregulation and disease, and iii) Nanotetrac may be a promising candidate for treating cancer, and resmetirom and VK2809 for steatohepatitis. Further, the use of L-T3 in the treatment of severely ill COVID-19 patients is critically discussed.

Manipulation of thyroid hormones in ruminants - a tool to understand their physiological role and identify their potential for increasing production efficiency

2002 ◽  
Vol 53 (3) ◽  
pp. 259 ◽  
Author(s):  
D. Villar ◽  
S. M. Rhind ◽  
J. R. Arthur ◽  
P. J. Goddard
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Production Efficiency ◽  
Hormone Replacement ◽  
Animal Health ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Physiological Role ◽  
Antithyroid Drugs ◽  
Few Data

Manipulations of thyroid hormone secretion and function can be used to cure thyroidal deficiencies or overactivity and as a tool to investigate their physiological roles and identify potential protocols for enhancing animal performance. An essential approach to the investigation of thyroid hormone action involves the induction of hypothyroidal states. Methods of inducing hypothyroidal states in ruminants include thyroidectomy and treatment with thionamides. There are few data concerning the induction of an optimal degree of hypothyroidism for the study of thyroid function in ruminants, unlike the situation in rodents. The effects of hypothyroidism on the physiology of ruminants, and the relative merits of thyroidectomy or of treatment with thionamides to manipulate thyroid hormone profiles in them, are reviewed and discussed. Thyroidectomy in ruminants induces an acute, irreversible, hypothyroidal state. It also has indirect, predominantly adverse, effects on many physiological processes and impairs health. Thus, thyroidectomised (THX) animals cannot be sustained for long-term studies without thyroid hormone replacement. Antithyroid drugs of the thionamide class, on the other hand, have been used with success to induce varying degrees of hypothyroidism, predominantly less severe than those induced by thyroidectomy. The changes induced by drugs are reversible upon withdrawal of treatment. However, treatment may require daily administration of the drug for several weeks before stable plasma concentrations of thyroid hormone are achieved. Furthermore, at high doses, these drugs can have toxic side effects. It is concluded that the treatment regime of choice will depend on the objectives of the individual study. Knowledge of the activities of thyroid hormone metabolising, deiodinase enzymes in the target tissues is also required if the actions of some of these drugs, their physiological roles in modulation of the thyroid hormones, and, crucially, their potential effects on animal health and production are to be properly understood and exploited.

The Influence of Thyroid Hormone on Ca2+ Signaling Pathways during Embryonal Development

2021 ◽  
Vol 21 ◽  
Author(s):  
Joachim Krebs
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Brain Development ◽  
Regulation Of Gene Expression ◽  
Embryonic Stem Cell Line ◽  
Embryonic Stem ◽  
Fetal Brain ◽  
Mouse Embryonic Stem Cell ◽  
Dependent Manner ◽  
Transcription Activator

: Thyroid hormones influence brain development through regulation of gene expression. Ca2+-dependent gene expression is a major pathway controlled by the Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) which in turn is induced by the thyroid hormone T3 as also demonstrated in a mouse embryonic stem cell line. In addition, T3 is controlling the expression of neurexin, synaptotagmin2 (SYT2), synaptotagmin-related gene1 (SRG1) and a number of other genes, involved in neurotransmitter release in a Ca2+-dependent manner. It has been noticed that the development of dopaminergic neurons by evoking significant calcium entry occurs through TRPC calcium channels. It also was demonstrated that the T3-mediated development of an early neuronal network is characteristic for depolarizing GABAergic neurons concomitant with intracellular calcium transients. An important aspect of T3-dependent regulation of gene expression in the developing brain is its modulation by the transcription activator COUP-TF1. Regulation of alternative splicing by CaMKIV is another important aspect for embryonal neural development since it can lead to the expression of PMCA1a, the neuronal specific isoform of the plasma membrane calcium pump. Maternal hypothyroidism or CaMKIV deficiency can have a severe influence on fetal brain development.

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