Placental 5-Deiodinase Activity and Fetal Thyroid Hormone Economy Are Unaffected by Selenium Deficiency in the Rat

Both a genetic or acquired neonatal thyroid hormone (TH) deficiency may result in a profound mental disability that is often accompanied by deafness. The existence of various TH-sensitive periods during inner ear development and general success of delayed, corrective TH treatment was investigated by treating pregnant and lactating rats with the goitrogen methimazole (MMI). We observed that for the establishment of normal hearing ability, maternal TH, before fetal thyroid gland function on estrus days 17–18, is obviously not required. Within a crucial time between the onset of fetal thyroid gland function and the onset of hearing at postnatal day 12 ( P12), any postponement in the rise of TH-plasma levels, as can be brought about by treating lactating mothers with MMI, leads to permanent hearing defects of the adult offspring. The severity of hearing defects that were measured in 3- to 9-mo-old offspring could be increased with each additional day of TH deficiency during this critical period. Unexpectedly, the active cochlear process, assayed by distortion product otoacoustic emissions (DPOAE) measurements, and speed of auditory brain stem responses, which both until now were not thought to be controlled by TH, proved to be TH-dependent processes that were damaged by a delay of TH supply within this critical time. In contrast, no significant differences in the gross morphology and innervation of the organ of Corti or myelin gene expression in the auditory system, detected as myelin basic protein (MBP) and proteolipid protein (PLP) mRNA using Northern blot approach, were observed when TH supply was delayed for few days. These classical TH-dependent processes, however, were damaged when TH supply was delayed for several weeks. These surprising results may suggest the existence of different TH-dependent processes in the auditory system: those that respond to corrective TH supply (e.g., innervation and morphogenesis of the organ of Corti) and those that do not, but require T3 activity during a very tight time window (e.g., active cochlear process, central processes).

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Thyroid hormones and fetal neurological development

Journal of Endocrinology ◽

10.1530/joe-10-0444 ◽

2011 ◽

Vol 209 (1) ◽

pp. 1-8 ◽

Cited By ~ 116

Author(s):

J Patel ◽

K Landers ◽

H Li ◽

R H Mortimer ◽

K Richard

Keyword(s):

Thyroid Hormone ◽

Cell Membrane ◽

Hormone Receptors ◽

Developmental Stages ◽

Fetal Brain ◽

Neurological Development ◽

Thyroid Hormone Metabolism ◽

Pituitary Thyroid Axis ◽

Fetal Thyroid ◽

Type 3

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 (T4) 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. T4 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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The Effect of Selenium Deficiency on Plasma Thyroid Hormone Concentrations and on Hepatic Tri-Iodothyronine Production

Trace Elements in Man and Animals 6 ◽

10.1007/978-1-4613-0723-5_20 ◽

1988 ◽

pp. 59-60

Author(s):

John R. Arthur ◽

Fergus Nicol ◽

Geoffrey J. Beckett

Keyword(s):

Thyroid Hormone ◽

Selenium Deficiency

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Maternal and placental responses before preterm birth: adaptations to increase fetal thyroid hormone availability?

The Journal of Maternal-Fetal & Neonatal Medicine ◽

10.1080/14767058.2018.1449199 ◽

2018 ◽

Vol 32 (16) ◽

pp. 2746-2757 ◽

Cited By ~ 2

Author(s):

An Eerdekens ◽

Lies Langouche ◽

Fabian Güiza ◽

Johan Verhaeghe ◽

Gunnar Naulaers ◽

...

Keyword(s):

Preterm Birth ◽

Thyroid Hormone ◽

Fetal Thyroid

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SP521THE EFFECT OF SELENIUM DEFICIENCY ON THYROID HORMONE AND CARDIOVASCULAR DISEASES IN PATIENTS WITH PERITONEAL DIALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx151.sp521 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii304-iii304

Author(s):

Hwa Young Lee ◽

Eun Kyoung Lee ◽

Jong Tae Cho ◽

Chang Hyun Park ◽

So Mi Kim

Keyword(s):

Peritoneal Dialysis ◽

Cardiovascular Diseases ◽

Thyroid Hormone ◽

Selenium Deficiency

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Effect of excessive iodine exposure on the placental deiodinase activities and Hoxc8 expression during mouse embryogenesis

British Journal Of Nutrition ◽

10.1017/s0007114507691909 ◽

2007 ◽

Vol 98 (1) ◽

pp. 116-122 ◽

Cited By ~ 8

Author(s):

Xue F. Yang ◽

Jian Xu ◽

Huai L. Guo ◽

Xiao H. Hou ◽

Li P. Hao ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormone Receptor ◽

Skeletal Development ◽

Gene Expression Pattern ◽

Skeletal Malformation ◽

Thyroid Hormone Metabolism ◽

Deiodinase Activity ◽

Excessive Iodine ◽

Total Thyroxine

Excessive iodine induces thyroid dysfunction. However, the effect of excessive iodine exposure on maternal–fetal thyroid hormone metabolism and on the expression of genes involved in differentiation, growth and development is poorly understood. Since a thyroid hormone receptor response element was found in the Hoxc8 promoter region, Hoxc8 expression possibly regulated by excessive iodine exposure was firstly investigated. In the present study, Balb/C mice were given different doses of iodine in the form of potassium iodate (KIO3) at the levels of 0 (sterile water), 1·5, 3·0, 6·0, 12·0 and 24·0 μg/ml in drinking water for 4 months, then were mated. On 12·5 d postcoitum, placental type 2 and type 3 deiodinase activities and fetal Hoxc8 expression were determined. The results showed that excessive iodine exposure above 1·5 μg/ml resulted in an increase of total thyroxine and a decrease of total triiodothyronine in the serum of maternal mice, which was mainly associated with the inhibition of type 1 deiodinase activity in liver and kidney. Placental type 2 deiodinase activity decreased, showing an inverse relationship with maternal thyroxine level. Hoxc8 mRNA and protein expression at 12·5 d postcoitum embryos were down regulated. Because Hoxc8 plays an important role in normal skeletal development, this finding provides a possible explanation for the skeletal malformation induced by excessive iodine exposure and also provides a new clue to study the relationship between iodine or thyroid hormones and Hox gene expression pattern.

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Fetal Thyroid Hormone Level at Birth Is Associated with Fetal Growth

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-2814 ◽

2011 ◽

Vol 96 (6) ◽

pp. E934-E938 ◽

Cited By ~ 60

Author(s):

Beverley M. Shields ◽

Beatrice A. Knight ◽

Anita Hill ◽

Andrew T. Hattersley ◽

Bijay Vaidya

Keyword(s):

Birth Weight ◽

Thyroid Hormone ◽

Cord Blood ◽

Thyroid Function ◽

Fetal Growth ◽

Late Gestation ◽

Third Trimester ◽

Free T4 ◽

Skeletal Size ◽

Fetal Thyroid

Context: Thyroid function is known to play an important role in fetal neurological development, but its role in regulating fetal growth is not well established. Overt maternal and fetal thyroid disorders are associated with reduced birth weight. We hypothesized that, even in the absence of overt thyroid dysfunction, maternal and fetal thyroid function influence fetal growth. Aim: In normal, healthy pregnancies, we aimed to assess whether fetal thyroid hormone at birth (as measured in cord blood) is associated with fetal growth. We also aimed to study whether fetal thyroid hormone at birth is associated with maternal thyroid hormone in the third trimester. Methods: In 616 healthy mother-child pairs, TSH, free T4 (FT4), and free T3 (FT3) were measured in mothers at 28 wk gestation and in umbilical cord blood at birth. Birth weight, length, head circumference, and tricep and bicep skinfold thicknesses were measured on the babies. Results: Cord FT4 was associated with birth weight (r = 0.25; P < 0.001), length (r = 0.17; P < 0.001), and sum of skinfolds (r = 0.19; P < 0.001). There were no associations between birth measurements and either cord TSH or cord FT3. Maternal FT4 and cord FT4 were correlated (r = 0.14; P = 0.0004), and there were weaker negative associations between maternal TSH and cord FT4 (r = −0.08; P = 0.04) and FT3 (r = −0.10; P = 0.01). Conclusion: Associations between cord FT4 and birth size suggest that fetal thyroid function may be important in regulating fetal growth, both of skeletal size and fat. The correlation between third-trimester maternal FT4 and cord FT4 supports the belief that maternal T4 crosses the placenta even in late gestation.

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Characterization of rat iodothyronine sulfotransferases

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00046.2003 ◽

2003 ◽

Vol 285 (3) ◽

pp. E592-E598 ◽

Cited By ~ 24

Author(s):

Monique H. A. Kester ◽

Ellen Kaptein ◽

Thirza J. Roest ◽

Caren H. van Dijk ◽

Dick Tibboel ◽

...

Keyword(s):

Thyroid Hormone ◽

Rat Brain ◽

Rat Liver ◽

Rat Kidney ◽

Female Rat ◽

Reversible Inactivation ◽

Fetal Thyroid ◽

Important Pathway ◽

Brain Cytosol

Sulfation appears to be an important pathway for the reversible inactivation of thyroid hormone during fetal development. The rat is an often used animal model to study the regulation of fetal thyroid hormone status. The present study was done to determine which sulfotransferases (SULTs) are important for iodothyronine sulfation in the rat, using radioactive T4, T3, rT3, and 3,3′-T2 as substrates, 3′-phosphoadenosine-5′-phosphosulfate (PAPS) as cofactor, and rat liver, kidney and brain cytosol, and recombinant rat SULT1A1, -1B1, -1C1, -1E1, -2A1, -2A2, and -2A3 as enzymes. Recombinant rat SULT1A1, -1E1, -2A1, -2A2, and -2A3 failed to catalyze iodothyronine sulfation. For all tissue SULTs and for rSULT1B1 and rSULT1C1, 3,3′-T2 was by far the preferred substrate. Apparent Km values for 3,3′-T2 amounted to 1.9 μM in male liver, 4.4 μM in female liver, 0.76 μM in male kidney, 0.23 μM in male brain, 7.7 μM for SULT1B1, and 0.62 μM for SULT1C1, whereas apparent Km values for PAPS showed less variation (2.0-6.9 μM). Sulfation of 3,3′-T2 was inhibited dose dependently by other iodothyronines, with similar structure-activity relationships for most enzymes except for the SULT activity in rat brain. The apparent Km values of 3,3′-T2 in liver cytosol were between those determined for SULT1B1 and -1C1, supporting the importance of these enzymes for the sulfation of iodothyronines in rat liver, with a greater contribution of SULT1C1 in male than in female rat liver. The results further suggest that rSULT1C1 also contributes to iodothyronine sulfation in rat kidney, whereas other, yet-unidentified forms appear more important for the sulfation of thyroid hormone in rat brain.

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