Acute Changes in Maternal Thyroid Hormone Induce Rapid and Transient Changes in Gene Expression in Fetal Rat Brain

Dowling, Amy L.S.; Martz, Gabriel U.; Leonard, Jack L.; Zoeller, R. Thomas

doi:10.1523/jneurosci.20-06-02255.2000

Cited by 115 publications

(84 citation statements)

References 62 publications

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“…In our study, hypothyroid rats were obtained by continuous administration, from E16, of an anti-thyroid drug (MTU) that inhibited both maternal and fetal thyroid glands. Although recent studies show that thyroid hormone regulates gene expression in fetal rat brain (Alvarez-Dolado et al, 1999;Dowling et al, 2000), we saw no clear influence of thyroid hormone on microglial development during late fetal stages. The distribution of the cells in newborn hypothyroid rats and, more specifically, their density in the cingulate cortex were normal.…”

Section: Thyroid Hormone Favors Microglia Expansion: Early Postnatal contrasting

confidence: 99%

Regulation of Microglial Development: A Novel Role for Thyroid Hormone

et al. 2001

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The postnatal development of rat microglia is marked by an important increase in the number of microglial cells and the growth of their ramified processes. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebrain regions of developing rats rendered hypothyroid by prenatal and postnatal treatment with methyl-thiouracil. Microglial processes were markedly less abundant in hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily injections of 3,5,3Ј-triiodothyronine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life.Reverse transcription-PCR and immunological analyses indicated that cultured cortical ameboid microglial cells expressed the ␣1 and ␤1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morphogenetic effects of thyroid hormone observed in situ, T3 favored the survival of cultured purified microglial cells and the growth of their processes. These results demonstrate that thyroid hormone promotes the growth and morphological differentiation of microglia during development.

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Section: Thyroid Hormone Favors Microglia Expansion: Early Postnatal contrasting

confidence: 99%

Regulation of Microglial Development: A Novel Role for Thyroid Hormone

et al. 2001

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“…In addition, A1254 increased the expression of Oct-1 mRNA in the fetal brain but had no effect on the expression of NSP-C (145). NSP-C is a splicing variant of NSP-A, which we have shown is not regulated by thyroid hormone in the E16 cortex (70,76). Importantly, the same doses of A1254 that significantly reduced circulating levels of thyroid hormone in neonatal animals had no effect on circulating levels of thyroid hormones in the dams.…”

mentioning

confidence: 61%

“…This definition was also applied to experimental studies to identify the developmental period during which thyroid hormone exerts a specific action. It is now generally accepted that there is no single critical period of thyroid hormone action on brain development, either in humans (15) or in animals (70). Rather, thyroid hormone acts on a specific development process during the period that the process is active.…”

Section: Thyroid Hormone and Brain Development In Experimental Animalsmentioning

confidence: 99%

Thyroid hormone, brain development, and the environment.

Zoeller

Dowling

Herzig

et al. 2002

Environ Health Perspect

233

157

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Thyroid hormone is essential for normal brain development. Therefore, it is a genuine concern that thyroid function can be altered by a very large number of chemicals routinely found in the environment and in samples of human and wildlife tissues. These chemicals range from natural to manufactured compounds. They can produce thyroid dysfunction when they are absent from the diet, as in the case of iodine, or when they are present in the diet, as in the case of thionamides. Recent clinical evidence strongly suggests that brain development is much more sensitive to thyroid hormone excess or deficit than previously believed. In addition, recent experimental research provides new insight into the developmental processes affected by thyroid hormone. Based on the authors' research focusing on the ability of polychlorinated biphenyls to alter the expression of thyroid hormone-responsive genes in the developing brain, this review provides background information supporting a new way of approaching risk analysis of thyroid disruptors. endemias occurring in different parts of the world have led to the proposal that the various symptoms of the two forms of cretinism arise from thyroid hormone deficits occurring at different developmental windows of vulnerability (15,17,49). Therefore, thyroid hormone appears to play an important role in fetal brain development, perhaps before the onset of fetal thyroid function.The second type of pathological situation is that of subtle, undiagnosed maternal hypothyroxinemia. The concept and definition of maternal hypothyroxinemia were developed in a series of papers by . Low thyroid hormone was initially defined empirically-those pregnant women with the lowest butanol-extractable iodine among all pregnant women (55,57). This work was among the first to document an association between subclinical hypothyroidism in pregnant women and neurological function of the offspring. After the development of radioimmunoassay for thyroid hormone, Pop et al. (58) found that the presence of antibodies to thyroid peroxidase in pregnant women, independent of thyroid hormone levels per se, is associated with significantly lower IQ in the offspring. Subsequent studies have shown that children born to women with thyroxine (T 4 ) levels in the lowest 10 th percentile of the normal range had a higher risk of low IQ and attention deficit (25). Excellent recent reviews discuss these studies in detail (24,57,59). Taken together, these studies present strong evidence that maternal thyroid hormone plays a role in fetal brain development before the onset of fetal thyroid function, and that thyroid hormone deficits in pregnant women can produce irreversible neurological effects in their offspring (18,19,22,37,(60)(61)(62). Thyroid Hormone and Brain Development in Experimental AnimalsConsiderable research using experimental animals has provided important insight into the mechanisms and consequences of thyroid hormone action in brain development. The body of this work is far too extensive to review here but has been rev...

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“…Additionally, there is no single critical period of thyroid hormone action in the developmental brain of the fetal rat (Dowling et al, 2000). In the tadpole of Lithobates sylvaticus, TRβ expression levels in the brain at climax increased 5-fold compared with premetamorphic stages (Navarro-Martin et al, 2012).…”

Section: Analysis Of Rctrα and Rctrβ During Metamorphosismentioning

confidence: 99%

Identification of thyroid hormone receptors α and β genes and their expression profiles during metamorphosis in Rana chensinensis*

Du¹,

Wang²,

Liang³

et al. 2017

Turk J Zool

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To explore the role of thyroid hormones in organ remodeling during the metamorphosis of amphibians, the cDNAs of two thyroid hormone receptors (TRα and TRβ) in Rana chensinensis were identified. The 1257 bp of rcTRα cDNA encoding 418 amino acids and the 1122 bp of rcTRβ cDNA encoding 373 amino acids were cloned. Their polypeptide sequences contain two highly conserved cysteine-rich zinc fingers in the DNA-binding domain, while rcTRβ is 42 amino acids shorter in its A/B domain when compared with rcTRα. Fifty-five amino acids differed between the TRα and TRβ domains. The rcTRα and rcTRβ mRNA levels in the liver, brain, skin, and tail of tadpoles were analyzed via qRT-PCR during metamorphosis. The results showed that the changes of rcTRα mRNA levels were moderate while those of rcTRβ were dramatic in all 4 tissues during metamorphosis. In addition, the levels of rcTRβ mRNA were relatively low at premetamorphosis and reached a peak around the climax. Tissue-specific expression of rcTRα and rcTRβ suggests that thyroid hormones play various roles in different organs or tissues at different developmental stages of metamorphosis.

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Acute Changes in Maternal Thyroid Hormone Induce Rapid and Transient Changes in Gene Expression in Fetal Rat Brain

Cited by 115 publications

References 62 publications

Regulation of Microglial Development: A Novel Role for Thyroid Hormone

Regulation of Microglial Development: A Novel Role for Thyroid Hormone

Thyroid hormone, brain development, and the environment.

Identification of thyroid hormone receptors α and β genes and their expression profiles during metamorphosis in Rana chensinensis*

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