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Low Dose Exposure to Di-2-Ethylhexylphthalate in Juvenile Rats Alters the Expression of Genes Related with Thyroid Hormone Regulation

Title
Low Dose Exposure to Di-2-Ethylhexylphthalate in Juvenile Rats Alters the Expression of Genes Related with Thyroid Hormone Regulation
Authors
Kim, MinjeongJeong, Ji SeongKim, HyunjiHwang, SeungwooPark, Il-HyunLee, Byung-ChulYoon, Sung IlJee, Sun HaNam, Ki TookLim, Kyung-Min
Ewha Authors
임경민김민정
SCOPUS Author ID
임경민scopus; 김민정scopusscopus
Issue Date
2018
Journal Title
BIOMOLECULES & THERAPEUTICS
ISSN
1976-9148JCR Link

2005-4483JCR Link
Citation
BIOMOLECULES & THERAPEUTICS vol. 26, no. 5, pp. 512 - 519
Keywords
Phthalatedi-2-ethylhexylphthalate (DEHP)ThyroidJuvenile toxicityThyroid hormoneProliferation
Publisher
KOREAN SOC APPLIED PHARMACOLOGY
Indexed
SCIE; SCOPUS; KCI WOS scopus
Document Type
Article
Abstract
Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.
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DOI
10.4062/biomolther.2018.076
Appears in Collections:
약학대학 > 약학과 > Journal papers
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