Thyroid hormone action during brain development: More questions than answers

Horn, Sigrun; Heuer, Heike

doi:10.1016/j.mce.2009.09.008

Cited by 173 publications

(123 citation statements)

References 95 publications

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“…Furthermore, D3KO mice are born hypothyroid with impaired growth and fertility (Galton 2005). They exhibit excessive T 3 -responsive gene activation during development and reduced activation later in life (Horn & Heuer 2010).…”

Section: Deiodination Of Thyroid Hormonesmentioning

confidence: 99%

“…For thyroid hormone to gain access to the brain during maturation, it must pass through many different cell types which express the various cell membrane transporters. For rodents, the preferred route of TH entry is through the cerebral circulation and its blood-brain barrier, with some thyroid hormone entering the cerebrospinal fluid (CSF) via the choroid plexus (Dratman et al 1991, Horn & Heuer 2010). The T 4 -binding protein, transthyretin, produced in significant amounts by the choroid plexus, has been implicated in this transport, and transthyretin may be involved in delivery of CSF thyroid hormone to the brain (Patel et al 2010).…”

Section: Thyroid Hormone Transporters In the Brainmentioning

confidence: 99%

“…It is believed that the TRs found in these regions mediate the biological effects of T 3 that has been locally generated from transported maternal T 4 , early in gestation. Conversely, TRb isoforms are expressed more postnatally within specific neuronal populations such as hippocampal pyramidal and granule cells, paraventricular hypothalamic neurons, and cerebellar Purkinje cells (Bradley et al 1989, Horn & Heuer 2010. Studies in TRb KO mice have shown that these isoforms are predominant in mediating thyroid hormone effects on the development of the vision and auditory systems (Jones et al 2003).…”

Section: Tr Genes and Activitymentioning

confidence: 99%

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Thyroid hormones and fetal neurological development

Patel¹,

Landers²,

Li³

et al. 2011

Journal of Endocrinology

193

128

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The development of fetal thyroid function is dependent on the embryogenesis, differentiation, and maturation of the thyroid gland. This is coupled with evolution of the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism, resulting in the regulation of thyroid hormone action, production, and secretion. Throughout gestation there is a steady supply of maternal thyroxine (T 4 ) which has been observed in embryonic circulation as early as 4 weeks post-implantation. This is essential for normal early fetal neurogenesis. Triiodothyronine concentrations remain very low during gestation due to metabolism via placental and fetal deiodinase type 3. T 4 concentrations are highly regulated to maintain low concentrations, essential for protecting the fetus and reaching key neurological sites such as the cerebral cortex at specific developmental stages. There are many known cell membrane thyroid hormone transporters in fetal brain that play an essential role in regulating thyroid hormone concentrations in key structures. They also provide the route for intracellular thyroid hormone interaction with associated thyroid hormone receptors, which activate their action. There is a growing body of experimental evidence from rats and humans to suggest that even mild maternal hypothyroxinemia may lead to abnormalities in fetal neurological development. Our review will focus on the ontogeny of thyroid hormone in fetal development, with a focus on cell membrane transporters and TR action in the brain.

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Section: Deiodination Of Thyroid Hormonesmentioning

confidence: 99%

Section: Thyroid Hormone Transporters In the Brainmentioning

confidence: 99%

Section: Tr Genes and Activitymentioning

confidence: 99%

See 1 more Smart Citation

Thyroid hormones and fetal neurological development

Patel¹,

Landers²,

Li³

et al. 2011

Journal of Endocrinology

193

128

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“…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 the maturation of somatic tissues essential for survival immediately at birth. The important role of thyroid hormones in brain development is not considered here as this has been reviewed extensively in recent years (Horn & Heuer 2010, Patel et al 2011, Puig-Domingo & Vila 2013, Stenzel & Huttner 2013). …”

Section: Introductionmentioning

confidence: 99%

Thyroid hormones in fetal growth and prepartum maturation

Forhead

Fowden

2014

Journal of Endocrinology

341

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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“…Therefore, it is possible that the overlap between some of the symptoms of these two diseases contributes to the susceptibility to AD for patients who have been diagnosed with hypothyroidism. Several studies have shown that T3 is essential for healthy brain development, maturation, and function [22][23][24][25][26]. Studies using embryonic and adult mice demonstrated that T3 plays a vital role in the development and maintenance of basal forebrain cholinergic neurons which are typically altered by AD [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Thyroid Hormone Enhances Neurite Outgrowth in Neuroscreen 1 Cells

et al. 2018

Int J Biomed Investig

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Thyroid hormone action during brain development: More questions than answers

Cited by 173 publications

References 95 publications

Thyroid hormones and fetal neurological development

Thyroid hormones and fetal neurological development

Thyroid hormones in fetal growth and prepartum maturation

Thyroid Hormone Enhances Neurite Outgrowth in Neuroscreen 1 Cells

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