Our previous research has identified granulin (grn) and p130 genes as sex steroidinducible genes in the rat hypothalamus, which might be involved in sexual differentiation of the brain. Phthalate esters that are used as plasticizers and also found at low levels in foods such as dairy products are often mentioned as suspected endocrine disrupters. The purpose of the present study is to elucidate whether perinatal exposure to dinbutyl phthalate (DBP), diisononyl phthalate (DINP) and di2ethylhexyl adipate (DEHA) affects hypothalamic sex steroidinducible genes. The present study assessed the effects of perinatal exposure to DBP, DINP and DEHA on sex steroid hormones levels and hypothalamic grn and p130 mRNA expressions at postnatal day (PND) 3 and 7. Pregnant rats were fed a soyfree diet containing 20, 200, 2,000 and 10,000 ppm of DBP, 40, 400, 4,000 and 20,000 ppm of DINP, or 480, 2,400 and 12,000 ppm of DEHA from gestational day (GD) 15 to GD 3 or 7. At PND 3 and 7, perinatal exposure to these chemicals did not substantially affect serum concentrations of testosterone and estradiol. At PND 3, the expression of grn mRNA levels in males was decreased by DEHA, and that of p130 was decreased by DBP, DINP and DEHA, though the effects were not dosedependent. At PND 7, the expression of grn gene in female pups was increased by higher doses of DBP and all the doses, except for 4,000 ppm, of DINP, while that in male pups decreased by 480 and 12,000 ppm of DEHA. Hypothalamic expression of p130 mRNA in males was increased by lower doses of DBP and all the doses of DINP, whereas that of females was decreased by 480 and 2,400 ppm of DEHA. These results suggest that these chemicals may affect the expression of grn and p130 genes by directly acting on the hypothalamus, thus leading to inappropriate expression of these genes.

ABSTRACT  INTRODUCTION  MATERIALS AND METHODS  RESULTS  DISCUSSION  REFERENCES

• Hwi-Cheul Lee(Animal Biotechnology Division, National Livestock Research Institute, RDA, Suwon 441-706, Korea)
• Gi-Sun lm.(Animal Biotechnology Division, National Livestock Research Institute, RDA, Suwon 441-706, Korea)
• Hak Jae Chung.(Animal Biotechnology Division, National Livestock Research Institute, RDA, Suwon 441-706, Korea)
• Poong-Yeon Lee(Animal Biotechnology Division, National Livestock Research Institute, RDA, Suwon 441-706, Korea)
• Jin-Ki Park(Animal Biotechnology Division, National Livestock Research Institute, RDA, Suwon 441-706, Korea)
• Won-Kyong Chang(Animal Biotechnology Division, National Livestock Research Institute, RDA, Suwon 441-706, Korea)
• Boh-Suk Yang(Animal Biotechnology Division, National Livestock Research Institute, RDA, Suwon 441-706, Korea)
• Keitaro Yamanouchi(Department of Veterinary Physiology, Veterinary Medical Science, Tokyo University, Tokyo 11 3-86.57, Japan)
• Masugi Nishihara(Department of Veterinary Physiology, Veterinary Medical Science, Tokyo University, Tokyo 11 3-86.57, Japan, Corresponding author)