한국발생생물학회지:발생과생식 (Development and Reproduction)

  • 제18권4호
  • /
  • Pages.187-195
  • /
  • 2014
  • /
  • 2465-9525(pISSN)
  • /
  • 2465-9541(eISSN)
한국발생생물학회 (The Korean Society of Developmental Biology)
권호 표지
DOI QR코드

DOI QR Code

Disturbance in Testosterone Production in Leydig Cells by Polycyclic Aromatic Hydrocarbons

  • Oh, Seunghoon (Dept. of Physiology, College of Medicine, Dankook University)
  • 투고 : 2014.11.03
  • 심사 : 2014.11.10
  • 발행 : 2014.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Polycyclic aromatic hydrocarbons (PAHs), which are ubiquitous in the air, are present as volatile and particulate pollutants that result from incomplete combustion. Most PAHs have toxic, mutagenic, and/or carcinogenic properties. Among PAHs, benzo[a]pyrene (B[a]P) and dimethylbenz[a]anthracene (DMBA) are suspected endocrine disruptors. The testis is an important target for PAHs, yet effects on steroidogenesis in Leydig cells are yet to be ascertained. Particularly, disruption of testosterone production by these chemicals can result in serious defects in male reproduction. Exposure to B[a]P reduced serum and intratesticular fluid testosterone levels in rats. Of note, the testosterone level reductions were accompanied by decreased steroidogenic acute regulatory protein (StAR) and $3{\beta}$-hydroxysteroid dehydrogenase isomerase ($3{\beta}$-HSD) expression in Leydig cells. B[a]P exposure can decrease epididymal sperm quality, possibly by disturbing the testosterone level. StAR may be a key steroidogenic protein that is targeted by B[a]P or other PAHs.

키워드

참고문헌

  1. Adamsson A, Simanainen U, Viluksela M, Paranko J, Toppari J (2009) The effects of 2,3,7,8-tetrachlorodibenzop-dioxin on foetal male rat steroidogenesis. Int J Androl 32:575-585. https://doi.org/10.1111/j.1365-2605.2008.00900.x
  2. Akingbemi BT, Ge R, Klinefelter GR, Zirkin BR, Hardy MP (2004a) Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proc Natl Acad Sci U S A 101:775-780. https://doi.org/10.1073/pnas.0305977101
  3. Akingbemi BT, Sottas CM, Koulova AI, Klinefelter GR, Hardy MP (2004b) Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells. Endocrinology 145:592-603. https://doi.org/10.1210/en.2003-1174
  4. Akingbemi BT, Youker RT, Sottas CM, Ge R, Katz E, Klinefelter GR, Zirkin BR, Hardy MP (2001) Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl) phthalate. Biol Reprod 65:1252-1259. https://doi.org/10.1095/biolreprod65.4.1252
  5. Archibong AE, Ramesh A, Niaz MS, Brooks CM, Roberson SI, Lunstra DD (2008) Effects of benzo(a)pyrene on intra-testicular function in F-344 rats. Int J Environ Res Public Health 5:32-40. https://doi.org/10.3390/ijerph5010032
  6. Badawi AF, Cavalieri EL, Rogan EG (2000) Effect of chlorinated hydrocarbons on expression of cytochrome P450 1A1, 1A2 and 1B1 and 2- and 4-hydroxylation of 17beta-estradiol in female Sprague-Dawley rats. Carcinogenesis 21:1593-1599. https://doi.org/10.1093/carcin/21.8.1593
  7. Beischlag TV, Luis Morales J, Hollingshead BD, Perdew GH (2008) The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukaryot Gene Expr 18:207-250. https://doi.org/10.1615/CritRevEukarGeneExpr.v18.i3.20
  8. Buters J, Quintanilla-Martinez L, Schober W, Soballa VJ, Hintermair J, Wolff T, Gonzalez FJ, Greim H (2003) CYP1B1 determines susceptibility to low doses of 7,12-dimethylbenz[a]anthracene-induced ovarian cancers in mice: correlation of CYP1B1-mediated DNA adducts with carcinogenicity. Carcinogenesis 24:327-334. https://doi.org/10.1093/carcin/24.2.327
  9. Cavalieri EL, Higginbotham S, RamaKrishna NV, Devanesan PD, Todorovic R, Rogan EG, Salmasi S (1991) Comparative dose-response tumorigenicity studies of dibenzo [alpha,l]pyrene versus 7,12-dimethylbenz[alpha]anthracene, benzo-[alpha]pyrene and two dibenzo[alpha,l]-pyrene dihydrodiols in mouse skin and rat mammary gland. Carcinogenesis 12:1939-1944. https://doi.org/10.1093/carcin/12.10.1939
  10. Cerniglia CE (1984) Microbial metabolism of polycyclic aromatic hydrocarbons. Adv Appl Microbiol 30:31-71. https://doi.org/10.1016/S0065-2164(08)70052-2
  11. Chauvigne F, Menuet A, Lesne L, Chagnon MC, Chevrier C, Regnier JF, Angerer J, Jegou B (2009) Time- and dose-related effects of di-(2-ethylhexyl) phthalate and its main metabolites on the function of the rat fetal testis in vitro. Environ Health Perspect 117:515-521. https://doi.org/10.1289/ehp.11870
  12. Cheng SC, Hilton BD, Roman JM, Dipple A (1989) DNA adducts from carcinogenic and noncarcinogenic enantiomers of benzo[a]pyrene dihydrodiol epoxide. Chem Res Toxicol 2:334-340. https://doi.org/10.1021/tx00011a011
  13. Chung JY, Kim YJ, Kim JY, Lee SG, Park JE, Kim WR, Yoon YD, Yoo KS, Yoo YH, Kim JM (2011) Benzo[a] pyrene reduces testosterone production in rat Leydig cells via a direct disturbance of testicular steroidogenic machinery. Environ Health Perspect 119:1569-1574. https://doi.org/10.1289/ehp.1003391
  14. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC (2009) Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 30:293-342. https://doi.org/10.1210/er.2009-0002
  15. Ellis GB, Desjardins C, Fraser HM (1983) Control of pulsatile LH release in male rats. Neuroendocrinology 37:177-183. https://doi.org/10.1159/000123540
  16. Epstein LF, Orme-Johnson NR (1991) Acute action of luteinizing hormone on mouse Leydig cells: accumulation of mitochondrial phosphoproteins and stimulation of testosterone synthesis. Mol Cell Endocrinol 81:113-126. https://doi.org/10.1016/0303-7207(91)90210-J
  17. Fukuzawa NH, Ohsako S, Wu Q, Sakaue M, Fujii-Kuriyama Y, Baba T, Tohyama C (2004) Testicular cytochrome P450scc and LHR as possible targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the mouse. Mol Cell Endocrinol 221:87-96. https://doi.org/10.1016/j.mce.2004.02.005
  18. Goldman R, Enewold L, Pellizzari E, Beach JB, Bowman ED, Krishnan SS, Shields PG (2001) Smoking increases carcinogenic polycyclic aromatic hydrocarbons in human lung tissue. Cancer Res 61:6367-6371.
  19. Gray LE Jr, Ostby J, Furr J, Price M, Veeramachaneni DN, Parks L (2000) Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci 58:350-365. https://doi.org/10.1093/toxsci/58.2.350
  20. Gray LE Jr, Ostby J, Monosson E, Kelce WR (1999) Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol Ind Health 15:48-64. https://doi.org/10.1177/074823379901500106
  21. Gray LE Jr, Ostby JS (1995) In utero 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters reproductive morphology and function in female rat offspring. Toxicol Appl Pharmacol 133:285-294. https://doi.org/10.1006/taap.1995.1153
  22. Haider SG (2004) Cell biology of Leydig cells in the testis. Int Rev Cytol 233:181-241. https://doi.org/10.1016/S0074-7696(04)33005-6
  23. Hardy MP, Gelber SJ, Zhou ZF, Penning TM, Ricigliano JW, Ganjam VK, Nonneman D, Ewing LL (1991) Hormonal control of Leydig cell differentiation. Ann NY Acad Sci 637:152-163. https://doi.org/10.1111/j.1749-6632.1991.tb27308.x
  24. Higginbotham S, RamaKrishna NV, Johansson SL, Rogan EG, Cavalieri EL (1993) Tumor-initiating activity and carcinogenicity of dibenzo[a,l]pyrene versus 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene at low doses in mouse skin. Carcinogenesis 14:875-878. https://doi.org/10.1093/carcin/14.5.875
  25. IARC (1985) Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Polynuclear aromatic hydrocarbons. Part 4: Bitumens, coal-tars and derived products, shale oil and soots. IARC, Lyon, France; 35.
  26. Kanter EM, Walker RM, Marion SL, Brewer M, Hoyer PB, Barton JK (2006) Dual modality imaging of a novel rat model of ovarian carcinogenesis. J Biomed Opt 11: 041123. https://doi.org/10.1117/1.2236298
  27. Kelce WR, Stone CR, Laws SC, Gray LE, Kemppainen JA, Wilson EM (1995) Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist. Nature 375:581-585. https://doi.org/10.1038/375581a0
  28. Kerr JB, Knell CM (1988) The fate of fetal Leydig cells during the development of the fetal and postnatal rat testis. Development 103:535-544.
  29. Kim YJ, Chung JY, Kim JY, Lee SG, Park JE, Oh S, Joo BS, Yoo KS, Yoo YH, Kim JM (2014) 7,12-Dimethylbenzanthracene reduces testosterone production in testicular Leydig cells. Manuscript in preparation.
  30. Knize MG, Salmon CP, Pais P, Felton JS (1999) Food heating and the formation of heterocyclic aromatic amine and polycyclic aromatic hydrocarbon mutagens/carcinogens. Adv Exp Med Biol 459:179-193. https://doi.org/10.1007/978-1-4615-4853-9_12
  31. Kozack RE, Loechler EL (1999) Molecular modeling of the major adduct of (+)-anti-B[a]PDE (N2-dG) in the eight conformations and the five DNA sequences most relevant to base substitution mutagenesis. Carcinogenesis 20:85-94. https://doi.org/10.1093/carcin/20.1.85
  32. Lawther PJ, Waller RE (1976) Coal fires, industrial emissions and motor vehicles as sources of environmental carcinogens. IARC Sci Publ 13:27-40.
  33. Lipsett MB, Wilson H, Kirschner MA, Korenman SG, Fishman LM, Sarfaty GA, Bardin CW (1966) Studies on Leydig cell physiology and pathology: secretion and metabolism of testosterone. Recent Prog Horm Res 22:245-281.
  34. Menzie CA, Potocki BB, Santodonato J (1992) Ambient concentrations and exposure to carcinogenic PAHs in the environment. Environ Sci Technol 26:1278-1283. https://doi.org/10.1021/es00031a002
  35. Mimura J, Fujii-Kuriyama Y (2003) Functional role of AhR in the expression of toxic effects by TCDD. Biochim Biophys Acta 1619:263-268. https://doi.org/10.1016/S0304-4165(02)00485-3
  36. Miyata M, Kudo G, Lee YH, Yang TJ, Gelboin HV, Fernandez-Salguero P, Kimura S, Gonzalez FJ (1999) Targeted disruption of the microsomal epoxide hydrolase gene. Microsomal epoxide hydrolase is required for the carcinogenic activity of 7,12-dimethylbenz[a]anthracene. J Biol Chem 274:23963-23968. https://doi.org/10.1074/jbc.274.34.23963
  37. Monosson E, Kelce WR, Lambright C, Ostby J, Gray LE Jr (1999) Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the development of androgen-dependent tissues, and alters androgen receptor function in the male rat. Toxicol Ind Health 15:65-79. https://doi.org/10.1177/074823379901500107
  38. Moore RW, Jefcoate CR, Peterson RE (1991) 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits steroidogenesis in the rat testis by inhibiting the mobilization of cholesterol to cytochrome P450scc. Toxicol Appl Pharmacol 109:85-97. https://doi.org/10.1016/0041-008X(91)90193-I
  39. Murono EP, Derk RC (2004) The effects of the reported active metabolite of methoxychlor, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane, on testosterone formation by cultured Leydig cells from young adult rats. Reprod Toxicol 19:135-146. https://doi.org/10.1016/j.reprotox.2004.06.010
  40. Mutoh J, Taketoh J, Okamura K, Kagawa T, Ishida T, Ishii Y, Yamada H (2006) Fetal pituitary gonadotropin as an initial target of dioxin in its impairment of cholesterol transportation and steroidogenesis in rats. Endocrinology 147:927-936. https://doi.org/10.1210/en.2005-1125
  41. Nebert DW, Dalton TP, Okey AB, Gonzalez FJ (2004) Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 279:23847-23850. https://doi.org/10.1074/jbc.R400004200
  42. Ohtake F, Fujii-Kuriyama Y, Kawajiri K, Kato S (2011) Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system. J Steroid Biochem Mol Biol 127:102-107. https://doi.org/10.1016/j.jsbmb.2011.03.007
  43. Park LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow NJ, Gray LE Jr (2000) The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 58:339-349. https://doi.org/10.1093/toxsci/58.2.339
  44. Payne AH, O'Shaughnessy PJ, In: Payne AH, Hardy MP, Russell LD (Eds.) (1996) The Leydig Cell. 1996 Cache River Press, Vienna, IL, pp 259-285.
  45. Schug TT, Janesick A, Blumberg B, Heindel JJ (2011) Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol 127:204-215. https://doi.org/10.1016/j.jsbmb.2011.08.007
  46. Sharpe RM (2006) Pathways of endocrine disruption during male sexual differentiation and masculinization. Best Pract Res Clin Endocrinol Metab 20:91-110. https://doi.org/10.1016/j.beem.2005.09.005
  47. Sharpe RM, Skakkebaek NE (2003) Male reproductive disorders and the role of endocrine disruption: advances in understanding and identification of areas for future research. Pure Appl Chem 75:2023-2038.
  48. Siiteri PK, Wilson JD (1974) Testosterone formation and metabolism during male sexual differentiation in the human embryo. J Clin Endocrinol Metab 38:113-125. https://doi.org/10.1210/jcem-38-1-113
  49. Sims RC, Overcash MR (1983) Fate of polynuclear aromatic compounds (PNAs) in soil-plant systems. Residue Rev 88:1-68.
  50. Skakkebaek NE, Rajpert-De Meyts E, Main KM (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 16:972-978. https://doi.org/10.1093/humrep/16.5.972
  51. Srogi K (2007) Monitoring of environmental exposure to polycyclic aromatic hydrocarbons: a review. Environ Chem Lett 5:169-195. https://doi.org/10.1007/s10311-007-0095-0
  52. Stocco DM (2000) The role of the StAR protein in steroidogenesis: challenges for the future. J Endocrinol 164: 247-253. https://doi.org/10.1677/joe.0.1640247
  53. Stocco DM (2001) StAR protein and the regulation of steroid hormone biosynthesis. Annu Rev Physiol 63: 193-213. https://doi.org/10.1146/annurev.physiol.63.1.193
  54. Thomas JA, Thomas MJ (1984) Biological effects of di-(2-ethylhexyl) phthalate and other phthalic acid esters. Crit Rev Toxicol 13:283-317. https://doi.org/10.3109/10408448409023761
  55. US EPA (1998) Endocrine disrupter screening and testing advisory committee (EDSTAC) final report. Washington, DC: United States Government; http://www.epa.gov/endo/pubs/edspoverview/finalrpt.htm
  56. US EPA (1999) Compendium of methods for the determination of toxic organic compounds in ambient air. Environmental Protection Agency, US Federal Register Compendium Method TO-13A:1-42.
  57. Walsh EL, Cuyler WK, McCullagh DR (1934) The physicologic maintenance of the male sex glands. Am J Physiol 107:508-512.
  58. Welshons WV, Thayer KA, Judy BM, Taylor JA, Curran EM, vom Saal FS (2003) Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Environ Health Perspect 111:994-1006. https://doi.org/10.1289/ehp.5494
  59. Wong C, Kelce WR, Sar M, Wilson EM (1995) Androgen receptor antagonist versus agonist activities of the fungicide vinclozolin relative to hydroxyflutamide. J Biol Chem 270:19998-20003. https://doi.org/10.1074/jbc.270.34.19998
  60. Yang SK, McCourt DW, Roller PP, Gelboin HV (1976) Enzymatic conversion of benzo(a)pyrene leading predominantly to the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyr-ene through a single enantiomer of r-7, t-8-dihydroxy-7,8-dihydrobenzo(a) pyrene. Proc Natl Acad Sci U S A 73 2594-2598. https://doi.org/10.1073/pnas.73.8.2594
  61. Yoshioka W, Peterson RE, Tohyama C (2011) Molecular targets that link dioxin exposure to toxicity phenotypes. J Steroid Biochem Mol Biol 127:96-101. https://doi.org/10.1016/j.jsbmb.2010.12.005
  62. Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, Woodruff TJ, Vom Saal FS (2012) Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society. Endocrinology 153:4097-4110. https://doi.org/10.1210/en.2012-1422