Best Practice & Research Clinical Endocrinology & Metabolism
Volume 20, Issue 1 , Pages 45-61 , March 2006

Endocrine-disrupting chemicals as modulators of sex steroid synthesis

  • Saffron A. Whitehead, PhD (Professor of Reproductive Endocrinology)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +44 208 8725 5360; fax: +44 208 8725 2993.
    • ,
  • Suman Rice, PhD (Post doctorate Yellow)

References 

  1. Sharpe RM. The ‘oestrogen hypothesis’—where do we stand now?. International Journal of Andrology. 2003;26:2–15
  2. Thomas JL, Duax WL, Addlagatta A, et al. Structure/function aspects of human 3β-hydroxysteroid dehydrogenase. Molecular and Cellular Endocrinology. 2004;215:73–82
  3. Luu-The V. Analysis and characteristics of multiple types of human 17β-hydroxysteroid dehydrogenases. The Journal of Steroid Biochemistry and Molecular Biology. 2001;76:143–151
  4. Wong CK, Keung WM. Bovine adrenal 3β-hydrogenase E.C.1.1.1.145)/5-ene-4ene isomerase (E>C>5.3.3.5.1); characterization and its inhibition by iosoflavones. The Journal of Steroid Biochemistry and Molecular Biology. 1999;71:191–202
  5. Ohno S, Shinoda S, Toyoshima S, et al. Effects of favonoid phytochemicals on cortisol production and on activities of steroidogenic enzymes in human adrenocortical H295R cells. The Journal of Steroid Biochemistry and Molecular Biology. 2002;80:3355–3363
  6. Ohno S, Matsukmoto N, Watanade M, Nakajin S. Flavonoid inhibition of overexpressed human 3β-hydroxysteroid dehydrogenase type II. The Journal of Steroid Biochemistry and Molecular Biology. 2004;88:175–182
  7. Le Bail JC, Champavier Y, Chulia AJ, Habrioux G. Effects of phytoestrogens on aromatase, 3β and 17β-hydroxysteroid dehydrogenase activities and human breast cancer cells. Life Science. 2000;66:1281–1291
  8. Mesiano S, Katz SL, Lee JY, Jaffe RB. Phytoestrogens alter adrenocortical functions: genistein and daidzein suppress glucocorticoid and stimulate androgen production by cultured adrenal cortical cells. Journal of Clinical Endocrinology and Metabolism. 1999;84:2443–2448
  9. Kaplanski O, Shemesh M, Berman A. Effects of phyto-oestrogens on progesterone synthesis by isolated bovine granulosa cells. Journal of Endocrinology. 1981;89:343–348
  10. Lacey M, Bohday J, Shamara MR, et al. Dose–response effects of phytoestrogens on the activity and expression of 3β-hydroxysteroid dehydrogenase and aromatase in human granulosa-luteal cells. The Journal of Steroid Biochemistry and Molecular Biology; in press. 2005; 96: 279–286
  11. Nejaty H, Lacey M, Whitehead SA. Differing effects of endocrine-disrupting chemicals on basal and FSH-stimulated progesterone production in rat granulosa-luteal cells. Experimental Biology and Medicine. 2001;226:570–576
  12. Mäkelä S, Poutanen M, Lehtimäki J, et al. Estrogen specific 17β-hydroxysteriod oxidoreductase type 1 (E.C.1.1.1.62) as a possible target for the action of phytoestrogens. Proceedings of the Society for Experimental Biology and Medicine. 1995;208:51–59
  13. Whitehead SA, Lacey M. Pytoestrogens inhibit aromatase but not 17β-hydroxysteroid dehydrogenase (HSD) type 1 in human granulosa-luteal cells; evidence for FSH induction of 17β-HSD. Human Reproduction. 2003;18:487–494
  14. Whitehead SA, Cross JE, Burden C, Lacey M. Acute and chronic effects of genistein tyrphostin and lavendustin A on steroid synthesis in luteinized human granulose cells. Human Reproduction. 2002;17:589–594
  15. Krazeisen A, Breitling R, Möller G, Adamski J. Phytoestrogens inhibit human 17β-hydroxysteroid dehydrogenase type 5. Molecular and Cellular Endocrinology. 2001;171:151–162
  16. Harris RM, Wood DM, Bottomley L, et al. Phytoestrogens are potent inhibitors of estrogen sulfation; implications for breast cancer risk and treatment. The Journal of Clinical Endocrinology and Metabolism. 2005;89:1779–1787
  17. Huang Z, Fasco MJ, Kaminsky LS. Inhibition of estrone sulfatase in human liver microsomes by quercetin and other flavonoids. The Journal of Steroid Biochemistry and Molecular Biology. 1997;63:9–15
  18. Almstrup K, Fernández MF, Petersen JH, et al. Dual effects of phytoestrogens result in U-shaped dose-response curves. Environmental Health Perspectives. 2002;110:743–748
  19. Sanderson JT, Hordijk J, Denison MS, et al. Induction and inhibition of aromatase (CYP19) activity by natural and synthetic flavonoid compounds in H295R human adrenocortical carcinoma cells. Toxicological Sciences. 2004;82:70–79
  20. Myllymäki S, Haavisto T, Vainio M, et al. In vitro effects of diethylstilbestrol, genistein, 4-tert-butylphenol, and 4-tert-octylphenol on steroidogenic activity of isolated immature rat ovarian follicles. Toxicol and Applied Pharmacol. 2005;204:69–80
  21. Brueggemeier RQ, Gu X, Mobley JA, et al. Effects of phytoestrogens and synthetic combinatorial libraries on aromatase, estrogen biosynthesis and metabolism. Annals of the New York Academy of Sciences. 2001;948:51–66
  22. Le Bail JC, Laroche T, Marre-Fournier F, Habrioux . Aromatase and 17β-hydroxysteriod dehydrogenase inhibition by flavonoids. Cancer Letters. 1998;133:101–110
  23. Shimada H, Uchida M, Okawara T, et al. Inhibitory effects of flavonoids on the reduction of progesterone to 20α-hydroxyprogesterone in rat liver. The Journal of Steroid Biochemistry and Molecular Biology. 2005;93:73–79
  24. Kellis JT, Vickery LE. Inhibition of human estrogen synthetase (aromatase) by flavones. Science. 1984;225:1032–1034
  25. Jeong HJ, Shin YG, Kim IH, Pezzuto JM. Inhibition of aromatase activity by flavanoids. Archives of Pharmacalogical Research. 1999;22:309–312
  26. Luu-The V, Dufort K, Pelletier G, Labrie F. Type 5 17β-hydroxysteriod dehydrogenase: its role in the formation of androgens in women. Molecular and Cellular Endocrinology. 2001;171:77–82
  27. Adlercreutz H, Bannwart C, Wähàlä T, et al. Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens. The Journal of Steroid Biochemistry and Molecular Biology. 1993;44:147–153
  28. Wang C, Mäkelä T, Hase T, et al. Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes. The Journal of Steroid Biochemistry and Molecular Biology. 1994;50:205–215
  29. Saarinen NM, Huovinen R, Warri A, et al. Enterolactone inhibits the growth of 7,12-dimethylbenz(a) anthracene-induced mammary carcinomas in the rat. Molecular Cancer Therapeutics. 2002;1:869–876
  30. Tiemann U, Tomek W, Schneider F, Vanselow J. Effects of the mycotoxins α- and β-zearalenol on regulation of progesterone synthesis in cultured granulosa cells from porcine ovaries. Reproductive Toxicology. 2003;17:673–681
  31. Mäkelä S, Poutanen M, Kostian ML, et al. Inhibition of 17β-hydroxysteriod oxidoreductase by flavonoids in breast and prostate cancer cells. Society for Experimental Biology and Medicine. 1998;217:310–316
  32. Keung W-M. Dietary estrogenic isoflavones are potent inhibitors of β-hydroxysteroid dehydrogenase of P. testosteronii. Biochemical and Biophysical Research Communications. 1995;215:1137–1144
  33. Kao Y-C, Zhou C, Sherman M, et al. Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: a site directed mutagenesis study. Environmental Health Perspectives. 1998;106:85–92
  34. Collins BM, McLachlan JA, Arnold SF. The oestrogenic and antioestrogenic activities of phytochemicals with the human estrogen receptor expressed in yeast. Steroids. 1997;65:365–372
  35. Kuiper GGJM, Lemmen JG, Carlssson B, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology. 1998;139:4252–5263
  36. Sohoni P, Sumpter JP. Several environmental oestrogens are also anti-androgens. The Journal of Endocrinology. 1998;158:327–339
  37. Sharpe RM, Irvine DS. How strong is the evidence of a link between environmental chemicals and adverse effects on human reproductive health?. British Medical Journal. 2004;328:447–451
  38. Younglai EV, Holloway AC, Lim GE, Foster WG. Synergistic effects between FSH and 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (p,p′-DDE) on human granulose cell aromatase activity. Human Reproduction. 2004;19:1089–1093
  39. You L, Sar M, Bartolucci E, et al. Induction of hepatic aromatase by p,p′DDE in adult male rats. Molecular and Cellular Endocrinology. 2001;178:207–214
  40. Sanderson JT, Boerma J, Lansbergen GWA, van den Berg M. Induction and inhibition of aromatase (CYP19) activity by various classes of pesticides in H295R human adrenocortical carcinoma cells. Toxicology and Applied Pharmacology. 2002;182:44–54
  41. Alléra A, Lo S, King I, et al. Impact of androgenic/antiandrogenic compounds (AAC) on human sex steroid metabolizing key enzymes. Toxicology. 2004;205:75–85
  42. Chedrese PJ, Feyles F. The diverse mechanism of action of dichlorodiphenyldichloroethylene (DDE) and methoxychlor in ovarian cells in vitro. Reproductive Toxicology. 2001;15:693–698
  43. Fent K, Woodin BR, Stegemna JJ. Effects of triphenyltin and other organotins on hepatic monooxygenase system in fish. Comparative Biochemistry and Physiology, Part C: Pharmacology, Toxicology and Endocrinology. 1998;121:277–288
  44. Walsh LP, Stocco DM. Effects of lindane on steroidogenesis and steroidogenic acute regulatory protein expression. Biology of Reproduction. 2000;63:1024–1033
  45. Sanderson JT, Boerma J, Lansbergen GWA, van den Berg M. Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes. Environmental Health Perspectives. 2001;109:1027–1031
  46. Zarn JA, Bruschweiler BJ, Schlatter JR. Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14α-demethylase and aromatase. Environmental Health Perspectives. 2003;111:255–261
  47. Trosken ER, Scholz K, Lutz RW, et al. Comparative assessment of the inhibition of recombinant human CYP19 (aromatase) by azoles used in agriculture and as drugs for humans. Endocrine Research. 2004;30:387–394
  48. Vinggaard AM, Hnida C, Breinholt V, Larsen JC. Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro. Toxicology in Vitro. 2000;14:227–234
  49. Odum J, Ashby J. Detection of aromatase inhibitors in vitro using rat ovary microsomes. Toxicology Letters. 2002;129:119–122
  50. Nativelle-Serpentini C, Richard S, Séralini G-E, et al. Aromatase activity modulation by lindane and bisphenol-A in human placental JEG-3 and transfected kidney E293 cells. Toxicology in Vitro. 2003;17:413–422
  51. Akingbemi BT, Sottas CM, Koulova AI, et al. 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. 2005;145:592–603
  52. Lovekamp TN, Davis BJ. Mono-(2-ethylhexyl) phthalate suppresses aromatase transcript levels and estradiol production in cultured rat granulosa cells. Toxicology and Applied Pharmacology. 2001;172:217–224
  53. Mazur W, Aldercreutz H. Overview of naturally occurring endocrine-active substances in the human diet in relation to human health. Nutrition. 2000;16:654–687
  54. Magiolinni M, Bonofiglio D, Marsico S, et al. Estrogen receptor α mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Molecular Pharmacology. 2001;60:595–602
  55. Barnes S. Phytoestrogens and breast cancer. Baillieres Clinical Endocrinology and Metabolism. 1998;12:559–579
  56. Chetrite GS, Pasqualini JR. The selective oestrogen enzyme modulator (SEEM) in breast cancer. The Journal of Steroid Biochemistry and Molecular Biology. 2001;76:95–104
  57. Boersma BJ, Barnes S, Kirk M, et al. Soy isoflavonoids and cancer—metabolism at the target site. Mutation Research. 2001;1:480–481
  58. Younglai EV, Foster WG, Hughes EG, et al. Levels of environmental contaminants in human follicular fluid, serum, and seminal plasmas of couples undergoing in vitro fertilization. Archives of Environmental Contamination and Toxicology. 2002;43:121–126
  59. Lo S, Alléra A, Albers P, et al. Dithioerythritol (DTE) prevents inhibitory effects of triphenyltin (TPT) on the key enzymes of the human sex steroid hormone metabolism. The Journal of Steroid Biochemistry and Molecular Biology. 2003;84:569–576
  60. Colon I, Caro D, Bourdony CJ, Rosario O. Identification of phthalate esters in the serum of young puerto rican girls with premature breast development. Environmental Health Perspectives. 2000;108:895–900
  61. Duty SM, Calafat AM, Silva MJ, et al. Phthalate exposure and reproductive hormones in adult men. Human Reproduction. 2005;20:604–610
  62. Ikezuki Y, Tsutsumi O, Takai Y, et al. Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Human Reproduction. 2002;17:2839–2841
  63. Richards JS. New signaling pathways for hormones and cyclic adenosine 3′,5′-monophosphate action in endocrine cells. Molecular Endocrinology. 2001;15:209–218
  64. Akiyama T, Ishida J, et al. Nakagawa.Genistein, a specific inhibitor of tyrosine-specific protein kinases. Journal of Biological Chemistry. 1997;262:5592–5595
  65. Nguyen TT, Tran E, Nguyen TH, et al. The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells. Carcinogenesis. 2004;25:647–659
  66. Whitehead SA, Lacey M. Protein tyrosine kinase activity of the phytoestrogen genistein and lavendustin A on progesterone synthesis in cultured ovarian cells of the rat. Fertility and Sterility. 2000;73:613–619
  67. Bulayeva NN, Watson CS. Xenoestrogen-induced ERK-1 and ERK-2 activation via multiple membrane-initiated signalling pathways. Environmental Health Perspectives. 2004;112:1481–1487
  68. Lovekamp-Swan T, Jetten AM, Davis BJ. Dual activation of PPARα and PPARγ by mono-(2-ethylhexyl) phthalate in rat ovarian granulosa cells. Molecular and Cellular Endocrinology. 2003;210:133–141
  69. Rice S, Lacey M, Mason, H, et al. Phytoestrogens inhibit mRNA expression and activity of aromatase in human granulosa-luteal (GL) cells. The Endocrine Society Abstracts: 2005; 87th Annual Meeting: P2-263.

PII: S1521-690X(05)00070-9

doi: 10.1016/j.beem.2005.09.003

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 20, Issue 1 , Pages 45-61 , March 2006

Article Tools

* Image Usage & Resolution