Thyroid Hormones and the Central Nervous System

Pasquini, Juana M.; Adamo, Ana M.

doi:10.1159/000112080

Cited by 78 publications

(44 citation statements)

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“…In developing mammals (including humans), a deficiency or excess of thyroid hormone (TH) in the developing brain during the fetal and neonatal periods can lead to morphologic and functional abnormalities (15)(16)(17)(18). The most severe form of TH deficiency in human fetus and neonate is the syndrome of cretinism.…”

Section: Discussionmentioning

confidence: 99%

Compound W, a 3,3′-Diiodothyronine Sulfate Cross-Reactive Substance in Serum from Pregnant Women—A Potential Marker for Fetal Thyroid Function

Huang

et al. 2007

Pediatr Res

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Compound W, a 3,3=-diiodothyronine sulfate (T 2 S) cross-reactive material in maternal serum, was found to be useful as a marker for fetal hypothyroidism. In the present report, we explored its biochemical properties and studied its concentrations in cord and in maternal serum obtained from various gestational periods and at term from different continents. Mean W concentrations, expressed as nmol/L T 2 S-equivalent, in maternal serum during gestation showed a moderate increase at 20 -26 wk (1.57 nmol/L) and an accelerated increase to 34 -40 wk (3.59 nmol/L). The mean serum level was relatively low in nonpregnant women (0.17 nmol/L). Compound W levels in cord and maternal serum at term were not significantly different among samples obtained from Taiwan compared with samples from the United States. The mean cord serum "corrected" (by hot acid digestion) concentrations of W were significantly higher than maternal serum concentrations at birth and were also higher in venous than in paired arterial samples, suggesting that the placenta may play a role in its production. We compared a total of 45 iodothyronine analogs by antibody, gel filtration, and HPLC chromatographic studies and found only one compound, N,N-dimethyl- E mploying a sensitive RIA for T 2 S, we found high concentrations in fetal and pregnant serum in humans (1). We further identified that this T 2 S-cross-reactive material is not authentic T 2 S and does not co-chromatograph with synthetic T 2 S on HPLC. Thus, the name Compound W was coined to represent this material in fetal and maternal serum (1). Levels increased with the progression of pregnancy and rapidly peaked before parturition. At delivery, a 20-fold increase in "T 2 S" was found compared with nonpregnant women and returned to baseline within 7-10 d. Serial measurements of serum W in pregnant women have been found to be useful as a noninvasive technique for the diagnosis of fetal hypothyroidism (2,3).The present study was undertaken to determine the normal distribution of elevated Compound W levels in different stages of pregnancy as well as from various geographic areas and correlate between paired maternal and cord blood samples, and to explore its origin and chemical structure. MATERIALS AND METHODS T 2 S RIA. 3,3=-T 2 S and [125 I]T 2 S were prepared by the method of Eelkman-Rooda and co-workers (4,5). T 2 S was further purified and quantitatively recovered by reverse-phase HPLC with a preparative column, as described previously (1,2,4).The T 2 S RIA procedure was a modification of the RIA described previously (1,2). Serum samples (0.2-1.0 mL) were extracted with 2 vol 95% ethanol (final concentration, 63%) before assay. Preliminary experiments showed that the extraction efficiency of T 2 S in serum exceeded 96%. Final T 2 S concentrations were not corrected for recovery. The lower limit of detection of the assay was 3.3 fmol (2 pg), or 33.1 pmol/L in a 300 L ethanol extract of serum. Intra-assay variations were 1.9 -9.1% and interassay variations were 6.0 -19.5%, depending on ...

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Section: Discussionmentioning

confidence: 99%

Compound W, a 3,3′-Diiodothyronine Sulfate Cross-Reactive Substance in Serum from Pregnant Women—A Potential Marker for Fetal Thyroid Function

Huang

et al. 2007

Pediatr Res

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“…For example, in the central nervous system, thyroid hormone deficiency results in a generalized delay in brain growth, while thyroid hormone excess accelerates neurogenic development (2,3,43). In both cases, the orderly progression of neuronal maturation through stages of proliferation, migration, differentiation, neurite outgrowth, synaptogenesis, and myelination is disrupted, with profound and irreversible consequences with respect to function.…”

Section: Discussionmentioning

confidence: 99%

“…However, the levels of thyroid hormones required for development and the timing of their appearance are critical; exposure of the embryo to excessive levels of these compounds is highly detrimental. In mammals, this can result in fetal malformations, growth retardation, craniosynostosis, and abnormal brain development that is manifested by learning disabilities and mental retardation (3)(4)(5)(6)(7)(8). In amphibia, premature exposure to exogenous thyroid hormones results in uncoordinated development that inevitably results in larval death (9).…”

Section: Introductionmentioning

confidence: 99%

Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase

Galton¹,

Bueno-Martínez²,

Hernández³

et al. 1999

J. Clin. Invest.

139

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Although thyroid hormones are critically important for the coordination of morphogenic processes in the fetus and neonate, premature exposure of the embryo to levels of the hormones present in the adult is detrimental and can result in growth retardation, malformations, and even death. We report here that the pregnant rat uterus expresses extremely high levels of the type 3 iodothyronine deiodinase (D3), which inactivates thyroxine and 3,3′,5-triiodothyronine by 5-deiodination. Both D3 mRNA and activity were present at the implantation site as early as gestational day 9 (E9), when expression was localized using in situ hybridization to uterine mesometrial and antimesometrial decidual tissue. At later stages of gestation, uterine D3 activity remained very high, and the levels exceeded those observed in the placenta and in fetal tissues. After days E12 and E13, as decidual tissues regressed, D3 expression became localized to the epithelial cells lining the recanalized uterine lumen that surrounds the fetal cavity. These findings strongly suggest that the pregnant uterus, in addition to the placenta, plays a critical role in determining the level of exposure of the fetus to maternal thyroid hormones.J. Clin. Invest. 103:979-987 (1999).

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“…Yet, it is more than likely that the observed BPA effects, combined with numerous biologically linked mechanisms, also occur in vivo, with the notion that in vivo, TRβ expression is restricted to specific ontogenetic states and is highly tissue specific (Bradley et al, 1994). Altogether, this idea is consonant with results from animal models that have shown that hypothyroidism during critical periods of development causes a variety of abnormalities in the central nervous system (Pasquini and Adamo, 1994;Martinez-Galan et al, 1997;Simorangkir et al, 1997), and that TRα and TRβ can compensate for each other's hypofunction. Finally, it should be noted that a growing body of evidence exists to show that BPA and other EDs increase intracellular reactive oxygen species and generate oxidative stress conditions in mitochondria and endoplasmic reticulum (Huc et al, 2012;Babu et al, 2013).…”

Section: Further Considerationsmentioning

confidence: 81%

Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture

Somogyi

Horváth

Tóth

et al. 2016

Acta Veterinaria Hungarica

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Thyroid hormones (THs) and oestrogens are crucial in the regulation of cerebellar development. TH receptors (TRs) mediate these hormone effects and are regulated by both hormone families. We reported earlier that THs and oestradiol (E 2 ) determine TR levels in cerebellar cell culture. Here we demonstrate the effects of low concentrations (10 -10 M) of the endocrine disruptor (ED) bisphenol A (BPA) on the hormonal (THs, E 2 ) regulation of TRα,β in rat cerebellar cell culture. Primary cerebellar cell cultures, glia-containing and glia-destroyed, were treated with BPA or a combination of BPA and E 2 and/or THs. Oestrogen receptor and TH receptor mRNA and protein levels were determined by real-time qPCR and Western blot techniques. The results show that BPA alone decreases, while BPA in combination with THs and/or E 2 increases TR mRNA expression. In contrast, BPA alone increased receptor protein expressions, but did not further increase them in combination with THs and/or E 2 . The modulatory effects of BPA were mediated by the glia; however, the degree of changes also depended on the specific hormone ligand used. The results signify the importance of the regulatory mechanisms interposed between transcription and translation and raise the possibility that BPA could act to influence nuclear hormone receptor levels independently of ligand-receptor interaction.Key words: Endocrine disruptors, thyroid receptor, transcription, translation, bisphenol A, rat cerebellum Thyroid hormones (THs) and oestrogens (mostly 17β-oestradiol, E 2 ) play critical roles in the regulation of central nervous system (CNS) development, in-* Corresponding author; Zsarnovszky.Attila@mkk.szie.hu; Phone: 0036 (28) 522-062/1620 (office); 0036 (30) 665-3717 (mobile); Fax: 0036 (28) 522-062

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Thyroid Hormones and the Central Nervous System

Cited by 78 publications

References 45 publications

Compound W, a 3,3′-Diiodothyronine Sulfate Cross-Reactive Substance in Serum from Pregnant Women—A Potential Marker for Fetal Thyroid Function

Compound W, a 3,3′-Diiodothyronine Sulfate Cross-Reactive Substance in Serum from Pregnant Women—A Potential Marker for Fetal Thyroid Function

Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase

Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture

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