Effects of Di(2-ethylhexyl) Phthalate on Regulation of Steroidogenesis or Spermatogenesis in Testes of Sprague-Dawley Rats

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概要

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• Di(2-ethylhexyl) phthalate (DEHP) used as a common plasticizer additive in the manufacture of plastics, such as polyvinyl chloride (PVC). This study examined the effect of DEHP on steroidogenesis or spermatogenesis in the testes of Sprague-Dawley male rats treated orally with 250, 500, 750 mg/kg over a 30-day period. The expression levels of the steroidogenic- or spermatogenic-related genes were analyzed in the testis using a reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. High doses of DEHP (500 and 750 mg/kg) significantly decreased the testicular sperm counts and daily sperm production (DSP). In addition, serum testosterone levels were significantly lower in the DEHP treatment groups than in the control. The mRNA levels of SR-B1, StAR, PBR and CYP17 increased in a dose-dependent manner. These increases were significant at 500 and 750 mg/kg. In the other hand, the mRNA levels of CYP19 decreased significantly in testes of rats exposed to DEHP 500 and 750 mg/kg. Dose-dependent decreases in Spag4 and LDHA mRNA in the testis were observed after DEHP exposure, while there was a significant decrease in thyroid hormone receptor (TR)α1 protein levels. High doses of DEHP significantly increased the expression of peroxisome proliferator-activated receptor (PPAR)-r and retinoid X receptor (RXR)-α protein but markedly decreased the expression of RXR-r. These results suggest that DEHP exposure can alter the expression of the spermatogenic- or steroidogenic-related genes resulting in a decrease in sperm production in the testis. This study is expected to be helpful in research examining the mechanisms for how DEHP reduces the expression pattern of the genes involved steroid hormone synthesis after chronic exposure to DEHP.

• 社団法人　日本薬学会の論文

著者

• LEE Ena

  College of Pharmacy, Pusan National University

• KIM Tae

  College of Pharmacy, Pusan National University

• CHOI Jae

  College of Pharmacy, Pusan National University

• JUNG Ki

  National Institute of Toxicological Research, Korea Food and Drug Administration

• KWACK Seung

  National Institute of Toxicological Research, Korea Food and Drug Administration

• KANG Tae

  National Institute of Toxicological Research, Korea Food and Drug Administration

• LEE Jaewon

  College of Pharmacy, Pusan National University

• LEE Byung

  Division of Toxicology, College of Pharmacy, Sungkyunkwan University

• KIM Hyung

  College of Pharmacy, Pusan National University

• LEE Young

  College of Veterinary Medicine, Seoul National University

• Kang Tae

  National Inst. Of Toxicological Res. Korea Food And Drug Administration

• Kim H

  College Of Pharmacy Pusan National University

• Han Soon

  National Institute of Toxicological Research, Korea Food and Drug Administration

• Han Soon

  National Inst. Of Toxicological Res. Korea Food And Drug Administration

• Kim Hyung

  College Of Oriental Medicine Institute Of Oriental Medicine Oriental Medical Science Center Kyung He

• Lee Jaewon

  College Of Pharmacy Pusan National University

• Choi Jae

  College Of Pharmacy Pusan National University

• Kim Kyu

  National Institute of Toxicological Research, Korea Food and Drug Administration

• Jung Ki

  National Institute Of Toxicological Research Korea Food And Drug Administration

• Lee Ena

  College Of Pharmacy Pusan National University

• Kim Tae

  College Of Pharmacy Chungbuk National University

• Kwack Seung

  National Institute Of Toxicological Research Korea Food And Drug Administration

• Kim Kyu

  National Inst. Of Toxicological Res. Korea Food And Drug Administration

• Lee Young

  College Of Bioscience Institute Of Biotechnology Department Of Bioscience And Biotechnology Sejong U

• Lee Byung

  Division Of Toxicology College Of Pharmacy Sungkyunkwan University

• Kim Hyung

  College of Information and Communication Engineering, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Republic of Korea

• Lee Byung

  Division of Drug Discovery Research, Korea Research Institute of Chemical Technology

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