Low Dose Exposure to Di-2-Ethylhexylphthalate in Juvenile Rats Alters the Expression of Genes Related with Thyroid Hormone Regulation
- 주제(키워드) Phthalate , di-2-ethylhexylphthalate (DEHP) , Thyroid , Juvenile toxicity , Thyroid hormone , Proliferation
- 주제(기타) Biochemistry & Molecular Biology; Pharmacology & Pharmacy
- 설명문(일반) [Kim, Minjeong; Lim, Kyung-Min] Ewha Womans Univ, Coll Pharm, Seoul 03760, South Korea; [Jeong, Ji Seong] Korea Inst Toxicol, Dev & Reprod Toxicol Res Grp, Daejeon 34114, South Korea; [Kim, Hyunji; Nam, Ki Took] Yonsei Univ, Coll Med, Brain Korea PLUS Project Med Sci 21, Severance Biomed Sci Inst, Seoul 03722, South Korea; [Hwang, Seungwoo] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr, Daejeon 34141, South Korea; [Park, Il-Hyun; Lee, Byung-Chul] GENECAST Co, Seongnam 05838, South Korea; [Yoon, Sung Il] Yonsei Univ, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul 03722, South Korea; [Yoon, Sung Il] Yonsei Univ, Grad Sch Publ Hlth, Inst Hlth Promot, Seoul 03722, South Korea; [Jee, Sun Ha] Lab Frontier Co, Anyang 14042, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- 발행기관 KOREAN SOC APPLIED PHARMACOLOGY
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156635
- 본문언어 영어
- Published As http://dx.doi.org/10.4062/biomolther.2018.076
초록/요약
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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