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

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.

Download Full-text

Differential effects of leptin and refeeding on the fasting-induced decrease of pituitary type 2 deiodinase and thyroid hormone receptor β2 mRNA expression in mice

Journal of Endocrinology ◽

10.1677/joe.1.06872 ◽

2006 ◽

Vol 190 (2) ◽

pp. 537-544 ◽

Cited By ~ 26

Author(s):

A Boelen ◽

J Kwakkel ◽

X G Vos ◽

W M Wiersinga ◽

E Fliers

Keyword(s):

Thyroid Hormone ◽

Mrna Expression ◽

Hormone Receptor ◽

Thyroid Hormone Receptor ◽

Hormone Metabolism ◽

Serum Leptin ◽

Thyroid Hormone Metabolism ◽

Hpt Axis ◽

As Effects

Profound changes in thyroid hormone metabolism occur in the central part of the hypothalamus–pituitary–thyroid (HPT) axis during fasting. Hypothalamic changes are partly reversed by leptin administration, which decreases during fasting. It is unknown to what extent leptin affects the HPT axis at the level of the pituitary. We, therefore, studied fasting-induced alterations in pituitary thyroid hormone metabolism, as well as effects of leptin administration on these changes. Because refeeding rapidly increased serum leptin, the same parameters were studied after fasting followed by refeeding. Fasting for 24 h decreased serum T3 and T4 and pituitary TSHβ, type 2deiodinase (D2), and thyroid hormone receptor β2 (TRβ2) mRNA expression. The decrease in D2 and TRβ2 mRNA expression was prevented when 20 μg leptin was administered twice during fasting. By contrast, the decrease in TSHβ mRNA expression was unaffected. A single dose of leptin given after 24 h fasting did not affect decreased TSHβ, D2, and TRβ2 mRNA expression, while 4 h refeeding resulted in pituitary D2 and TRβ2 mRNA expression as observed in control mice. Serum leptin, T3, and T4 after refeeding were similar compared with leptin administration. We conclude that fasting decreases pituitary TSHβ, D2, and TRβ2 mRNA expression, which (with the exception of TSHβ) can be prevented by leptin administration during fasting. Following 24 h fasting, 4 h refeeding completely restores pituitary D2 and TRβ2 mRNA expression, while a single leptin dose is ineffective. This indicates that other postingestion signals may be necessary to modulate rapidly the fasting-induced decrease in pituitary D2 and TRβ2 mRNA expression.

Download Full-text

Regional Decrease of Subcutaneous Adipose Tissue in Patients with Type 2 Familial Partial Lipodystrophy Is Associated with Changes in Thyroid Hormone Metabolism

Thyroid ◽

10.1089/thy.2009.0267 ◽

2010 ◽

Vol 20 (4) ◽

pp. 419-424 ◽

Cited By ~ 6

Author(s):

Joaquin Lado-Abeal ◽

Rosa-Maria Calvo ◽

Berta Victoria ◽

Isabel Castro ◽

Maria Jesus Obregon ◽

...

Keyword(s):

Adipose Tissue ◽

Thyroid Hormone ◽

Subcutaneous Adipose Tissue ◽

Hormone Metabolism ◽

Partial Lipodystrophy ◽

Thyroid Hormone Metabolism ◽

Familial Partial Lipodystrophy ◽

Subcutaneous Adipose

Download Full-text

Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A

Hormone and Metabolic Research ◽

10.1055/a-0919-3879 ◽

2019 ◽

Vol 51 (10) ◽

pp. 671-677 ◽

Cited By ~ 7

Author(s):

Maurício Martins da Silva ◽

Carlos Frederico Lima Gonçalves ◽

Leandro Miranda-Alves ◽

Rodrigo Soares Fortunato ◽

Denise P. Carvalho ◽

...

Keyword(s):

Adipose Tissue ◽

Thyroid Hormone ◽

Bisphenol A ◽

Brown Adipose Tissue ◽

Tissue Type ◽

Deiodinase Activity ◽

Brown Adipose

AbstractPlastics are ubiquitously present in our daily life and some components of plastics are endocrine-disrupting chemicals, such as bisphenol A and phthalates. Herein, we aimed to evaluate the effect of plastic endocrine disruptors on type 1 and type 2 deiodinase activities, enzymes responsible for the conversion of the pro-hormone T4 into the biologically active thyroid hormone T3, both in vitro and in vivo. Initially, we incubated rat liver type 1 deiodinase and brown adipose tissue type 2 deiodinase samples with 0.5 mM of the plasticizers, and the deiodinase activity was measured. Among them, only BPA was capable to inhibit both type 1 and type 2 deiodinases. Then, adult male Wistar rats were treated orally with bisphenol A (40 mg/kg b.w.) for 15 days and hepatic type 1 deiodinase and brown adipose tissue type 2 deiodinase activities and serum thyroid hormone concentrations were measured. In vivo bisphenol A treatment significantly reduced hepatic type 1 deiodinase activity but did not affect brown adipose tissue type 2 deiodinase activity. Serum T4 levels were higher in bisphenol A group, while T3 remained unchanged. T3/T4 ratio was decreased in rats treated with bisphenol A, reinforcing the idea that peripheral metabolism of thyroid hormone was affected by bisphenol A exposure. Therefore, our results suggest that bisphenol A can affect the metabolism of thyroid hormone thus disrupting thyroid signaling.

Download Full-text

Diminished hepatic triiodothyronine production in Gunn rats

Acta Endocrinologica ◽

10.1530/acta.0.1130281 ◽

1986 ◽

Vol 113 (2) ◽

pp. 281-288 ◽

Cited By ~ 2

Author(s):

J. R. Saltzman ◽

D. W. Clark ◽

R. D. Utiger

Keyword(s):

Thyroid Hormone ◽

Rat Liver ◽

Liver Homogenate ◽

Unconjugated Bilirubin ◽

Thyroid Hormone Metabolism ◽

Gunn Rats ◽

Deiodinase Activity ◽

Sediment Fraction ◽

Liver Homogenates

Abstract. The liver is a major site of conversion of thyroxine (T4) to the more active thyroid hormone 3,5,3'-triiodothyronine (T3). Hepatic T4 to T3 conversion is altered by a variety of pathological processes and pharmacological agents. We studied T4 to T3 conversion in glucuronyl transferase deficient homozygous Gunn rats because they have a hepatic enzyme abnormality which leads to hyperbilirubinaemia, and also because they have been reported to have alterations in thyroid hormone metabolism. An in vitro incubation system employing the 10 000 × g supernatant of liver homogenate was used, and T3 production was measured by radioimmunoassay. Experiments were done using substrate concentrations ranging from 0.56 to 20 μm, tissue protein in concentrations ranging from 0.625 to 20 mg and incubation times of 15 to 60 min. T3 production by liver homogenates from homozygous Gunn rats in these studies ranged from 29 to 70% of that produced by liver homogenates from phenotypically normal heterozygous Gunn rats. The deficit in hepatic T3 production by homozygous rats could not be overcome by increasing cofactor concentrations. After ultracentrifugation at 100 000 μ g, T4-5'-deiodinase activity was found primarily in the 100 000 × g sediment fraction. Homogygous rat liver 100 000 × g sediment T3 production was 55% of that of the heterozygous rat liver 100 000 × g sediment. Liver cytosol from both homozygous and heterozygous rats inhibited microsomal T4-5'-deiodinase activity similarly. Addition of unconjugated bilirubin to liver homogenates resulted in reduction of T3 production in livers from both homozygous and heterozygous rats. Thus the diminished capacity for hepatic conversion of T4 to T3 in homozygous Gunn rats may be due to inhibition of T4-5'-deiodinase activity by high endogenous levels of unconjugated bilirubin.

Download Full-text

Effect of Selenium on Thyroid Hormone Metabolism in Filial Cerebrum of Mice with Excessive Iodine Exposure

Biological Trace Element Research ◽

10.1385/bter:113:3:281 ◽

2006 ◽

Vol 113 (3) ◽

pp. 281-296 ◽

Cited By ~ 5

Author(s):

Huailan Guo ◽

Xuefeng Yang ◽

Jian Xu ◽

Xiaohui Hou ◽

Xiufa Sun

Keyword(s):

Thyroid Hormone ◽

Hormone Metabolism ◽

Thyroid Hormone Metabolism ◽

Excessive Iodine

Download Full-text

Lacking thyroid hormone receptor β gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

Journal of Endocrinology ◽

10.1677/joe-07-0601 ◽

2008 ◽

Vol 197 (1) ◽

pp. 151-158 ◽

Cited By ~ 20

Author(s):

J Kwakkel ◽

O Chassande ◽

H C van Beeren ◽

W M Wiersinga ◽

A Boelen

Keyword(s):

Thyroid Hormone ◽

Hormone Receptor ◽

Thyroid Hormone Receptor ◽

Hormone Metabolism ◽

Thyroid Hormone Metabolism ◽

Males And Females ◽

Induced Changes ◽

Thyroid Hormone Receptor Β

The downregulation of liver deiodinase type 1 (D1) is supposed to be one of the mechanisms behind the decrease in serum tri-iodothyronine (T3) observed during non-thyroidal illness (NTI). Liver D1 mRNA expression is positively regulated by T3, mainly via the thyroid hormone receptor (TR)β1. One might thus expect that lacking the TRβ gene would result in diminished downregulation of liver D1 expression and a smaller decrease in serum T3 during illness. In this study, we used TRβ−/− mice to evaluate the role of TRβ in lipopolysaccharide (LPS, a bacterial endotoxin)-induced changes in thyroid hormone metabolism. Our results show that the LPS-induced serum T3 and thyroxine and liver D1 decrease takes place despite the absence of TRβ. Furthermore, we observed basal differences in liver D1 mRNA and activity between TRβ−/− and wild-type mice and TRβ−/− males and females, which did not result in differences in serum T3. Serum T3 decreased rapidly after LPS administration, followed by decreased liver D1, indicating that the contribution of liver D1 during NTI may be limited with respect to decreased serum T3 levels. Muscle D2 mRNA did not compensate for the low basal liver D1 observed in TRβ−/− mice and increased in response to LPS in TRβ−/− and WT mice. Other (TRβ independent) mechanisms like decreased thyroidal secretion and decreased binding to thyroid hormone-binding proteins probably play a role in the early decrease in serum T3 observed in this study.

Download Full-text