Effects of Nonylphenol on CYP17 and CYP19 Expression in the Ovary of Sprague-Dawley Female Rats

Nonylphenol이 CYP17 및 CYP19발현에 미치는 영향

  • Kim Hee Jin (Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University) ;
  • Ahn Mee Young (Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University) ;
  • Kim In Young (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Kang Tae Seok (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Kim Tae Sung (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Kang Il Hyun (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Moon Hyun Ju (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Kil Hoyun (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Kim Soon Sun (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Lee Rhee Da (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Park Kui Lea (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Han Soon Young (Korea Food & Drug Administration, National Institute of Toxicological Research) ;
  • Kim Hyung Sik (Korea Food & Drug Administration, National Institute of Toxicological Research)
  • 김희진 (부산대학교 약학대학) ;
  • 안미영 (부산대학교 약학대학) ;
  • 김인영 (식품의약품안전청 국립독성연구원) ;
  • 강태석 (식품의약품안전청 국립독성연구원) ;
  • 김태성 (식품의약품안전청 국립독성연구원) ;
  • 강일현 (식품의약품안전청 국립독성연구원) ;
  • 문현주 (식품의약품안전청 국립독성연구원) ;
  • 기호연 (식품의약품안전청 국립독성연구원) ;
  • 김순선 (식품의약품안전청 국립독성연구원) ;
  • 이이다 (식품의약품안전청 국립독성연구원) ;
  • 박귀례 (식품의약품안전청 국립독성연구원) ;
  • 한순영 (식품의약품안전청 국립독성연구원) ;
  • 김형식 (식품의약품안전청 국립독성연구원)
  • Published : 2005.09.01

Abstract

Cytochrome P45O 17$\alpha$-hydroxylase (CYPI 7) and cytorhrome P45O aromata.ie (CYPI 9) are key steroidogenic enzymes in androgen and estrogen synthesis. ThiL study evaluated the effects of nonylphenol (NP) on CYP17 and CYP19 expression in the ovary of Sprague-Dawley rats. All female rats were administered orally with the vehicle (control, corn oil), diethylstilbestrol (DES, 5.0 $\mu$g/kg) and NP (50, 100, or 200 mg/kg/day), which was startinB when they were weaned at 21 days of age for 20 days. Twenty four hours after final dose, the animals were anelthetized with ether. Significant decreases in the uterus (wet weight) were observed with 5.0 $\mu$g/kg/day DES (78$\%$, of control) and 200 mg/kg/day NP (62$\%$ of control), respectively Additionally, ovarian weight was significantly decreased with 5.0 $\mu$g/kg/day DES (63$\%$ of control) and 200 mg/kg/day NP (72$\%$ of control). The serum estradiol levels were sligHtly lower in DES and high dose NP treatment groups, but the 74 levels were not affected by DES and NP. The expression of the ovarian CYP19 gene increased with low doses (50 and 100 mg/kg/day) of NP. while DES and high dose oi NP (200 mg/kg/day) did not affect on the CYP19 mRNA levels. In contrast to the CYP19 gene, the CYP17 gene expreLsion level was significantly down-regulated by the DES and 200 mg/ks/day NP. This result suggestE that NP inhibits ovarian estrogen synthelis by supprelsing CYP17 mRNA efprelsion, And different mechanisml might exist for the expression of Lteroidogenic CYP17 and CYP19 genes in the ovary of Sprague-Dawley rats in response to NP.

Keywords

References

  1. Aspden WJ, Rodgers RJ, Stocco DM, Scott PT, Wreford NG, Trigg TE, Walsh J and D'Occhino MJ. Changes in testicular steroidogenic acute regulatory (stat) protein, steroidogenic enzymes and testicular morphology associated with increased testosterone secretion in bulls receiving the luteinizing hormone releasing hormone agonist deslorelin. Domest Anim Endocrinol 1998; 15: 227-238 https://doi.org/10.1016/S0739-7240(98)00013-7
  2. Branham WS, Zehr DR and Sheehan DM. Differential sensitivity of rat uterine growth and epithelium hypertrophy to estrogens and antiestrogens. Proc Soc Exp Biol Med 1993; 203: 297-303
  3. Cook JC, Kaplan AM, Davis LG and O'connor JC. Development of a Tier I Screening Battery for Detecting Endocrine-Active Compounds (EACs). Regul Toxicol Pharmacol 1997; 26: 60-68 https://doi.org/10.1006/rtph.1997.1120
  4. Dasmahapatra AK, Wimpee BAB, Trewin AL, Wimpee CF, Ghorai JK and Hutz RJ. Demonstration of 2,3,7,8-tetrachlorodibenzo-p-dioxin attenuation of P450 steroidogenic enzyme mRNAs in rat granulosa cell in vitro by competitive reverse transcriptase - polymerase chain reaction assay. Mol Cell Endocrinol 2000; 164: 5-18 https://doi.org/10.1016/S0303-7207(00)00245-8
  5. EDSTAC. Endocrine Disruptor Screening and Testing Adversory Committee (EDST AC) Final Report, August 1998
  6. Goldman JM, Laws SC, Balchak SK, Cooper RL and Kavlock RJ. Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid activity in the female rat. A focus on the EDSTAC recommendations. Crit Rev Toxicol 2000; 30: 135 - 196 https://doi.org/10.1080/10408440091159185
  7. Hankinson SE, Willett WC, Manson JE, Colditz GA, Hunter DJ, Spiegelman D, Barbieri RL and Speizer FE. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 1998; 90: 1292-1299 https://doi.org/10.1093/jnci/90.17.1292
  8. Hurd C, Khattree N, Dinda S, Alban P and Moudgil VK. Regulation of tumor suppressor proteins, p53 and retinoblastoma, by estrogen and anti estrogens in breast cancer cells. Oncogene 1997; 15: 991-995 https://doi.org/10.1038/sj.onc.1201233
  9. Ikeda Y, Nagai A, Ikeda MA and Hayashi S. Neonatal estrogen exposure inhibits steroidogenesis in the developing rat ovary. Dev Dyn 2001; 221: 443-453 https://doi.org/10.1002/dvdy.1162
  10. Kavlock RJ. Overview of endocrine disruptor research activity in the United States. Chemosphere 1999; 39: 1227-1236 https://doi.org/10.1016/S0045-6535(99)00190-3
  11. Kim HS, Shin JH, Moon HJ, Kim TS, Kang IH, Seok JH, Kim IY, Park KL and Han SY. Evaluation of the 20day pubertal female assay in Sprague-Dawley rats treated with DES, tamoxifen, testosterone, and flutamide. Toxicol Sci 2002a; 67: 52-62 https://doi.org/10.1093/toxsci/67.1.52
  12. Kim HS, Shin JH, Moon HJ, Kang IH, Kim TS, Kim IY, Seok JH, Pyo MY and Han SY. Comparative estrogenic effects of p-nonylphenol by 3-day uterotrophic assay and female pubertal onset assay. Reprod Toxicol 2002b; 16: 259-268 https://doi.org/10.1016/S0890-6238(02)00028-X
  13. Kristensen VN, Kure EH, Erikstein B, Harada N and Borresen-Dale A. Genetic susceptibility and environmental estrogen-like compounds. Mutat Res 2001; 482: 77-82
  14. Laurenzana EM, Balasubramanian G, Weis C, Blaydes B, Newbold RR and Delclos KB. Effect of nonylphenol on serum testosterone levels and testicular steroidogenic enzyme activity in neonatal, pubertal, and adult rats. Chem Biol Interact 2002; 139: 23-41 https://doi.org/10.1016/S0009-2797(01)00291-5
  15. Majdic G, Sharpe RM, O'Shaughnessy PJ and Saunders PT. Expression of cytochrome P450 17alpha-hydroxylase/C17-20 lyase in the fetal rat testis is reduced by maternal exposure to exogenous estrogens. Endocrinology 1996; 137: 1063-1070 https://doi.org/10.1210/en.137.3.1063
  16. Myllymaki S, Haavisto T, Vainio M, Toppari J and Paranko J. In vitro effects of diethylstilbestrol, genistein, 4-tertbutylphenol, and 4-tert-octylphenol on steroidogenic activity of isolated immature rat ovarian follicles. Toxicol Appl Pharmacol 2005; 204: 69-80 https://doi.org/10.1016/j.taap.2004.08.009
  17. Nagai A, Ikeda Y, Aso T, Eto K and Ikeda MA. Exposure of neonatal rats to diethylstilbestrol affects the expression of genes involved in ovarian differentiation. J Med Dent Sci 2003; 50: 35-40
  18. Naylor CG, Mierure JP, Weeks JA, Castaldi FJ and Romano RR. Alkylphenol ethoxylates in the environment. J Am Oil Chemists Soc 1992; 69: 695-703 https://doi.org/10.1007/BF02635812
  19. Nimrod AC and Benson WH. Estrogenic effects of alkylphenol ethoxylates. Crit Rev Toxicol 1996; 26: 335 - 364 https://doi.org/10.3109/10408449609012527
  20. O'Connor JC, Frame SR, Biegel LB, Cook JC and Davis LG. Sensitivity of a Tier I screening battery compared to an in utero exposure for detecting the estrogen receptor agonist 17 beta-estradiol. Toxicol Sci 1998; 44: 169-184
  21. Odum J, Lefevre PA, Tittensor S, Paton D, Routledge EJ, Beresford NA, Sumpter JP and Ashby J. The rodent uterotrophic assay: critical protocol features studies with nonylphenol, and comparison with a yeast estrogenicity assay. Regul Toxicol Pharmacol 1997; 25: 176-188 https://doi.org/10.1006/rtph.1997.1100
  22. Odum J, Tinwell H, Van Miller J, Joiner R and Ashby J. The uterotrophic activity of nonylphenol in the rat is not mediated by aromatase enzyme induction. Toxicol Lett 2001; 118: 165-169 https://doi.org/10.1016/S0378-4274(00)00293-9
  23. Padykula HA, Fitzgerald M, Clark JH and Hardin JW. Nuclear bodies as structural indicators of estrogenic stimulation in uterine epithelial cells. Anat Res 1981; 201: 679-696 https://doi.org/10.1002/ar.1092010412
  24. Piacsek BE and Streur WJ. Effect of exposure to continuous light on estrogen-induced precocious sexual maturation in female rats. Neuro-endocrinology 1975; 18: 86-91 https://doi.org/10.1159/000122386
  25. Safe SH. Endocrine disruptors and human health-is there a problem? An update. Environ Health Perspect 2000; 108: 487-493 https://doi.org/10.2307/3454608
  26. Spornitz UM, Socin CD and Dravid AA. Estrous stage determination in rats by means of scanning electron microscopic images of uterine surface epithelium. Anat Res 1999; 254: 116-126 https://doi.org/10.1002/(SICI)1097-0185(19990101)254:1<116::AID-AR15>3.0.CO;2-X
  27. Thoreux-Manlay A, Le Goascogne C, Segretain D, Jegou B and Pinon-Lataillade, G. Lead affects steroidogenesis in rat Leydig cells in vivo and in vitro. Toxicology 1995; 103: 53-62 https://doi.org/10.1016/0300-483X(95)03107-Q
  28. You L, Chan SK, Bruce JM, Archiibeque-Engle S, Casanova M, Corton JC and Heck H. Modulation of testosterone-metabolizing hepatic cytochrome P-450 enzymes in developing Sprague- Dawley rats following in utero exposure to p, p'-DDE. Toxicol Appl Pharmacol 1999; 158: 197-205 https://doi.org/10.1006/taap.1999.8694