Effect of Thyroid Hormones on Neurons and Neurodevelopment

Prezioso, Giovanni; Giannini, Cosimo; Chiarelli, Francesco

doi:10.1159/000492129

Cited by 123 publications

(91 citation statements)

References 62 publications

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“…Phthalates can also affect the thyroid hormone balance (Araki et al, 2014) which leads to metabolic dysfunction in adults. Optimal maternal thyroid function during early pregnancy is essential for proper fetal brain development (Chen and Xue, 2018;Ghassabian and Trasande, 2018;Levie et al, 2018;Prezioso et al, 2018).…”

Section: Effect Of Phthalates As Endocrine Disrupting Chemicals On Emmentioning

confidence: 99%

Phthalate Exposure and Long-Term Epigenomic Consequences: A Review

et al. 2020

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Phthalates are esters of phthalic acid which are used in cosmetics and other daily personal care products. They are also used in polyvinyl chloride (PVC) plastics to increase durability and plasticity. Phthalates are not present in plastics by covalent bonds and thus can easily leach into the environment and enter the human body by dermal absorption, ingestion, or inhalation. Several in vitro and in vivo studies suggest that phthalates can act as endocrine disruptors and cause moderate reproductive and developmental toxicities. Furthermore, phthalates can pass through the placental barrier and affect the developing fetus. Thus, phthalates have ubiquitous presence in food and environment with potential adverse health effects in humans. This review focusses on studies conducted in the field of toxicogenomics of phthalates and discusses possible transgenerational and multigenerational effects caused by phthalate exposure during any point of the life-cycle.

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Section: Effect Of Phthalates As Endocrine Disrupting Chemicals On Emmentioning

confidence: 99%

Phthalate Exposure and Long-Term Epigenomic Consequences: A Review

et al. 2020

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“…THs play a very critical role on the central nervous system (CNS) ( Figure 2 ) as it is depicted by the severe effects on neuropsychological, cognitive development, and motor activity of children with congenital hypothyroidism, a condition known as cretinism ( 38 ). A perfect synergy between mother's THs actions and normal fetus thyroid development is necessary for neuronal differentiation, migration and proliferation ( 39 ). While TRα1 appears to be ubiquitous in CNS regions, TRβ1 is only present in hypothalamus, retina, pituitary gland, and cochlea in later stages of development ( 40 ).…”

Section: Effects Of Th S In the Liver And Central mentioning

confidence: 99%

“…Once THs have passed BBB, their local availability depends from the activity of the astrocytic type II deiodinase (D2) which converts T4 in T3. T3 is subsequently metabolized into 3,5-diiodothyronine (T2) by type 3 deiodinase (D3) in neurons ( 39 ).…”

Section: Effects Of Th S In the Liver And Central mentioning

confidence: 99%

Selective Thyroid Hormone Receptor-Beta (TRβ) Agonists: New Perspectives for the Treatment of Metabolic and Neurodegenerative Disorders

et al. 2020

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Thyroid hormones (THs) elicit significant effects on numerous physiological processes, such as growth, development, and metabolism. A lack of thyroid hormones is not compatible with normal health. Most THs effects are mediated by two different thyroid hormone receptor (TR) isoforms, namely TRα and TRβ, with the TRβ isoform known to be responsible for the main beneficial effects of TH on liver. In brain, despite the crucial role of TRα isoform in neuronal development, TRβ has been proposed to play a role in the remyelination processes. Consequently, over the past two decades, much effort has been applied in developing thyroid hormone analogs capable of uncoupling beneficial actions on liver (triglyceride and cholesterol lowering) and central nervous system (CNS) (oligodendrocyte proliferation) from deleterious effects on the heart, muscle and bone. Sobetirome (GC-1) and subsequently Eprotirome (KB2115) were the first examples of TRβ selective thyromimetics, with Sobetirome differing from the structure of thyronines because of the absence of halogens, biaryl ether oxygen, and amino-acidic side chain. Even though both thyromimetics showed encouraging actions against hypercholesterolemia, non-alcoholic steatohepatitis (NASH) and in the stimulation of hepatocytes proliferation, they were stopped after Phase 1 and Phase 2–3 clinical trials, respectively. In recent years, advances in molecular and structural biology have facilitated the design of new selective thyroid hormone mimetics that exhibit TR isoform-selective binding, and/or liver- and tissue-selective uptake, with Resmetirom (MGL-3196) and Hep-Direct prodrug VK2809 (MB07811) probably representing two of the most promising lipid lowering agents, currently under phase 2–3 clinical trials. More recently the application of a comprehensive panel of ADME-Toxicity assays enabled the selection of novel thyromimetic IS25 and its prodrug TG68, as very powerful lipid lowering agents both in vitro and in vivo . In addition to dyslipidemia and other liver pathologies, THs analogs could also be of value for the treatment of neurodegenerative diseases, such as multiple sclerosis (MS). Sob-AM2, a CNS- selective prodrug of Sobetirome has been shown to promote significant myelin repair in the brain and spinal cord of mouse demyelinating models and it is rapidly moving into clinical trials in humans. Taken together all these findings support the great potential of selective thyromimetics in targeting a large variety of human pathologies characterized by altered metabolism and/or cellular differentiation.

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“… 25 Studies have highlighted the association of thyroid dysfunction and neurocognitive development. 26 – 28 …”

Section: Thyroid Physiology During Pregnancymentioning

confidence: 99%

Thyroid disorders in subfertility and early pregnancy

Anandappa

Joshi

Polański

et al. 2020

Therapeutic Advances in Endocrinology

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Disorders of thyroid function are common in pregnancy and have implications for foetal and maternal health. Thyroid autoimmunity, as evidenced by the presence of elevated levels of anti-thyroid antibodies (anti-TPO and anti-Tg antibodies) is associated with an increased risk of miscarriage, though the mechanism remains poorly understood. There has been considerable focus on the implications and optimal management of pregnant women with thyroid disease, especially those undergoing assisted reproduction. Pregnancy results in significant changes in thyroid physiology and these need to be understood by clinicians involved in the care of pregnant women. Guidelines for the use of thyroxine and target thyroid function tests have been produced by international bodies but it is recognised that these predominantly reflect expert opinion rather than established evidence-based practice. Importantly a number of key clinical trials have been performed to aid understanding, particularly of the consequences of hypothyroidism for mother and baby, and the effectiveness of thyroid hormone use in autoimmune and subclinical hypothyroidism. This review summarises the current knowledge base and guidance for practice relating to thyroid disorders in pregnancy and subfertility.

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Effect of Thyroid Hormones on Neurons and Neurodevelopment

Cited by 123 publications

References 62 publications

Phthalate Exposure and Long-Term Epigenomic Consequences: A Review

Phthalate Exposure and Long-Term Epigenomic Consequences: A Review

Selective Thyroid Hormone Receptor-Beta (TRβ) Agonists: New Perspectives for the Treatment of Metabolic and Neurodegenerative Disorders

Thyroid disorders in subfertility and early pregnancy

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