Endocrine - Mimicking Phytoestrogens: Health Effects and Signaling

  • Published : 2004.12.01

Abstract

Phytoestrogens display estrogen-like activity because of their structural similarity to human estrogens and exhibit high affinity binding for the estrogen receptors (ERs). The prevalence of phytoestrogens in our diets and the biological effects that they may cause need to be fully examined. ER is the ancestral receptor from which all other steroid receptors have evolved. Although phytoestrogens serve specific signaling functions between the plants and insects, fungi, and bacteria, many chemical signals are often misinterpreted as estrogenic signals in non-target organisms such as vertebrates. There are no ERs in plants or in their most common partners, insects. However, Rhizobium soil bacteria have NodD proteins which is an intended target of phytoestrogen signaling and share genetic homology with the ER. These two evolutionarily distant receptors both recognize and respond to a shared group of chemical signals and ligands, including both agonists and antagonists. This review briefly summarizes estrogen and estrogen receptors, kinds of important phytoestrogens, their health effects as well as some of the evolutionary aspects of mechanism by which phytoestrogen mimics the endogenous ER signaling in our body.

Keywords

References

  1. Altavilla D, A Crisafulli, H Marini, M Esposito, R D'Anna, F Corrado, A Bitto and F Squadrito. 2004. Cardiovascular effects of the phytoestrogen genistein. Curr. Med. Chern. Cardiovasc. Hematol. Agents. 2:179-186 https://doi.org/10.2174/1568016043477297
  2. American Institute for Cancer Research. 1997. Food Nutrition and the Prevention of Cancer: A Global Perspective. World Cancer Research Fund, Washington
  3. Bagchi D, DK Das, A Tosaki, M Bagchi and SC Kothari. 2001. Benefits of resveratrol in women's health. Drugs Exp. Clin. Res. 27:233-248
  4. Bennetts HW, EJ Underwood and FL Shier. 1946. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust. Vet. J. 22:2-12 https://doi.org/10.1111/j.1751-0813.1946.tb15473.x
  5. Bianchini F and H Vainio. 2003. Wine and resveratrol : mechanisms of cancer prevention? Eur. J. Cancer Prevo 12:417-425 https://doi.org/10.1097/00008469-200310000-00011
  6. Bowers JL, VV Tyulmenkov, SC Jernigan and CM Klinge. 2000. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 141:3657-3667 https://doi.org/10.1210/en.141.10.3657
  7. Brownson DM, NG Azios, BK Fuqua, SF Dharmawardhane and TJ Mabry. 2002. Flavonoid effects relevant to cancer. J. Nutr. 132:3482S-3489S
  8. Carreau S. 2000. Estrogens and male reproduction. Folia Histochem. Cytobiol. 38:47 -52
  9. Collins-Burow BM, ME Burow, BN Duong and JA McLachlan. 2000. Estrogenic and antiestrogenic activities of flavonoid phytochemicals through estrogen eceptor binding-dependent and-independent mechanisms. Nutr. Cancer 38:229-244 https://doi.org/10.1207/S15327914NC382_13
  10. Creasy LL and MT Creasy. 1998. Grape chemistry and the significance of resveratrol : An Overview. Pharm. BioI. 36:8-14
  11. Cruz ML, WW Wong, F Mimouni, DL Hachey, KD Setchell, PD Klein and RC Tsang. 1994. Effects of infant nutrition on cholesterol synthesis rates. Pediatr. Res. 35:1 35-140 https://doi.org/10.1203/00006450-199402000-00001
  12. Dixon RA and D Ferreira. 2002. Genistein. Phytochemistry 60:205-211 https://doi.org/10.1016/S0031-9422(02)00116-4
  13. Duffy R, H Wiseman and SE File. 2003. Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones. Pharmacol. Biochem. Behav. 75:721-729 https://doi.org/10.1016/S0091-3057(03)00116-3
  14. File SE, N Jarrett, E Fluck, R Duffy, K Casey and H Wiseman. 2001. Eating soya improves human memory. Psychopharmacology 157:430-436 https://doi.org/10.1007/s002130100845
  15. Fox JE, M Starcevic, PE Jones, ME Burow and JA McLachlan. 2004. Phytoestrogen signaling and symbiotic gene activation are disrupted by endocrinedisrupting chemicals. Environ. Health Perspect. 112: 672-677 https://doi.org/10.1289/ehp.6456
  16. Fox JE, M Starcevic, KY Kow, ME Burow and JA McLachlan. 2001. Nitrogen fixation. Endocrine disrupters and flavonoid signalling. Nature 413:128-129
  17. Franke AA, LJ Custer, CM Cerna and KK Narala. 1994. Quantitation of phytoestrogens in legumes by HPLC. J. Agric. Food Chern. 42:1905-1913 https://doi.org/10.1021/jf00045a015
  18. Frigo DE, BN Duong, LI Melnik, LS Schief, BM CollinsBurow, DK Pace, et al. 2002. Flavonoid phytochemicals regulate activator protein-1 signal transduction pathways in endometrial and kidney stable cell lines. J. Nutr. 132:1848-1853
  19. Fritz WA, 1-E Eltoum, MS Cotroneo and CA Lamartiniere. 2002. Genistein alters growth but is not toxic to the rat prostate. J. Nutr. 132:3007-3011
  20. Fritz WA, J Wang and CA Lamartiniere. 1998. Dietary genistein: perinatal mammary cancer prevention, bio bioavailability and toxicity testing in the rat. Carcinogenesis 19:2151-2158 https://doi.org/10.1093/carcin/19.12.2151
  21. Gehm BD, JM McAndrews, PY Chien and JL Jameson. 1997. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc. Nat. Acad. Sci. USA. 94:14138-14143 https://doi.org/10.1073/pnas.94.25.14138
  22. Glitso LV, W Mazur, H Adlercreutz, K Whl, T Mkel, B Sandstrm and K Wahala. 2000. Intestinal metabolism of rye lignans in pigs. Br. J. Nutr. 84:429-437
  23. Gyorgypal Z and A Kondorosi. 1991. Homology of the ligand-binding regions of Rhizobium symbiotic regulatory protein NodD and vertebrate nuclear receptors. Mol. Gen. Genet. 226:337-340 https://doi.org/10.1007/BF00273624
  24. Hays J, JK Ockene, RL Brunner, JM Kotchen, JE Manson, RE Patterson, AK Aragaki, SA Shumaker, RG Brzyski, AZ LaCroix and IA Granek, Women's Health Initiative Investigators and BG Valanis. 2003. Effects of estrogen plus progestin on health-related quality of life. N. Engl. J. Med. 348:1835-1837 https://doi.org/10.1056/NEJMp030038
  25. Ho SC, SG Chan, Q Yi, E Wong and PC Leung. 2001. Soy intake and the maintenance of peak bone mass in Hong Kong Chinese women. J. Bone Miner. Res. 16:13631369 https://doi.org/10.1359/jbmr.2001.16.7.1363
  26. Hodis HN, WJ Mack and R Lobo. 2003. What is the cardioprotective role of hormone replacement therapy? Curro Atheroscler. Rep. 5:56-66 https://doi.org/10.1007/s11883-003-0069-z
  27. Horn-Ross PL, KJ Hoggatt and MM Lee. 2002. Phytoestrogens and thyroid cancer risk: the San Francisco Bay Area thyroid cancer study. Cancer Epidemiol. Biomarkers Prevo 11:4349
  28. Ishihara A, N Nishiyama, S Sugiyama and K Yamauchi. 2003. The effect of endocrine disrupting chemicals on thyroid hormone binding to Japanese quail transthyretin and thyroid hormone receptor. Gen. Compo Endocrinol. 134:36-43 https://doi.org/10.1016/S0016-6480(03)00197-7
  29. Kay RR. 1998. The biosynthesis of differentiation-inducing factor, a chlorinated signal molecule regulating Dietyostetium development. J. BioI. Chern. 273:2669-2675 https://doi.org/10.1074/jbc.273.5.2669
  30. Klinge CM, KE Risinger, MB Watts, V Beck, REder and A Jungbauer. 2003. Estrogenic activity in white and red wine extracts. J. Agric. Food Chern. 51:1850-1857 https://doi.org/10.1021/jf0259821
  31. Klotz DM, SC Hewitt, P Ciana, M Raviscioni, JK Lindzey, J Foley J, et at. 2002. Requirement of estrogen receptorin insulin-like growth factor-1 (IGF-I)-induced uterine responses and in vivo evidence for IGF-l/estrogen receptor cross-talk. J. BioI. Chern. 277:8531-8537 https://doi.org/10.1074/jbc.M109592200
  32. Krebs EE, KE Ensrud, R MacDonald and TJ Wilt. 2004. Phytoestrogens for treatment of menopausal symptoms: a systematic review. Obstet. Gynecol. 104:824-836 https://doi.org/10.1097/01.AOG.0000140688.71638.d3
  33. Kuiper GG, JG Lemmen, B Carlsson, JC Corton, SH Safe, PT van der Saag, B van der Burg and J - A Gustafsson. 1998. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor $\beta$. Endocrinology 139:42 52-4263 https://doi.org/10.1210/en.139.10.4252
  34. Kurzer MS. 2002. Hormonal effects of soy in premenopausal women and men. J. Nutr. 132:570S-573S
  35. Lemay A, S Dodin, N Kadri, H Jacques and J -C Forest. 2002. Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Obstet. Gynecol. 100:495-504 https://doi.org/10.1016/S0029-7844(02)02123-3
  36. Lucas EA, RD Wild, LJ Hammond, DA Khalil, S Juma, BP Daggy, BJ Stoecker and BH Arjmandi. 2002. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J. Clin. Endocrinol. Metab. 87:1527 -1532 https://doi.org/10.1210/jc.87.4.1527
  37. Macgregor JI and VC Jordan. 1998. Basic guide to the mechanisms of antiestrogen action. Pharmacol. Rev. 50:151-196
  38. Mannila E and A Talvitie. 1992. Stilbenes from Picea abies bark. Phytochemistry 31:3288-3289 https://doi.org/10.1016/0031-9422(92)83500-X
  39. Martin ME, M Haourigui, C Pelissero, C Benassayag and EA Nunez. 1996. Interactions between phytoestrogens and human sex steroid binding protein. Life Sci. 58:429436
  40. McCann SE, JL Freudenheim, JR Marshall and S Graham. 2003. Risk of human ovarian cancer is related to dietary intake of selected nutrients, Phytochemicals and Food Groups. J. Nutr. 133:1937-1942
  41. McCann SE, KB Moysich, JL Freudenheim, CB Ambrosone and PG Shields. 2002. The risk of breast cancer associated with dietary lignans differs by CYP17 genotype in women. J. Nutr. 132:3036-3041
  42. McLachlan JA. 2001. Environmental signaling: what embryos and evolution teach us about endocrine disrupting chemicals. Endocr. Rev. 22:319-341 https://doi.org/10.1210/er.22.3.319
  43. Mei J, SS Yeung and AW Kung. 2001. High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J. Clin. Endocrinol. Metab. 86:52175221 https://doi.org/10.1210/jc.86.11.5217
  44. Mentor-Marcel R, CA Lamartiniere, I-E Eltoum, NM Greenberg and A Elgavish. 2001. Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP). Cancer Res. 61:6777-6782
  45. Mitchell JH, E Cawood, D Kinniburgh, A Provan, AR Collins and DS Irvine. 2001. Effect of a phytoestrogen food supplement on reproductive health in normal males. Clin. Sci. (Lond.) 100:613-618 https://doi.org/10.1042/CS20000212
  46. Moriyama K, T Tagami, T Akamizu, T Usui, M Saijo, N Kanamoto, et al. 2002. Thyroid hormone action is disrupted by bisphenol A as an antagonist. J. Clin. Endocrinol. Metab. 87:5185-5190 https://doi.org/10.1210/jc.2002-020209
  47. Murrill W, N Brown, J Zhang, P Manzolillo, S Barnes and CA Lamartiniere. 1996. Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats. Carcinogenesis 17:1451-1457 https://doi.org/10.1093/carcin/17.7.1451
  48. Nilsson Sand JA Gustafsson. 2002. Biological role of estrogen and estrogen receptors. Crit. Rev. Biochem. Mol. BioI. 37:128
  49. Oberdorster E, MA Clay, DM Cottam, FA Wilmot, JA McLachlan and MJ Milner. 2001. Common phytochemicals are ecdysteroid agonists and antagonists: a possible evolutionary link between vertebrate and invertebrate steroid hormones. J. Steroid. Biochem. Mol. BioI. 77:229238 https://doi.org/10.1016/S0960-0760(01)00067-X
  50. Park OJ and JI Shin. 2002. Weight reduction and cardioprotective effects of phytoestrogens in rats. Proc. The Korean Nutrition Society Conf. p161
  51. Potter SM, JA Baum, H Teng, RJ Stillman, NF Shay and JW Erdman Jr. 1998. Soy protein and isoflavones : their effects on blood lipids and bone density in postmenopausal women. Am. J. Clin. Nutr. 68(Suppl):1375S-13 79S
  52. Powell RG, MR TePaske, RD Plattner, JF White and SL Clement. 1994. Isolation of resveratrol from Festuca versuta and evidence for the widespread occurrence of this stilbene in the poaceae. Phytochemistry 35:335-338 https://doi.org/10.1016/S0031-9422(00)94759-9
  53. Ramanathan L and WG Gray. 2003. Identification and characterization of a phytoestrogen-specific gene from the MCF-7 human breast cancer cell. Toxicol. Appl. Pharmacol. 191:107-117 https://doi.org/10.1016/S0041-008X(03)00221-7
  54. Razandi M, A Pedram, GL Greene and ER Levin. 1999. Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ER and $ER\beta$ expressed in chinese hamster ovary cells. Mol. Endocrinol. 13:307-319 https://doi.org/10.1210/me.13.2.307
  55. Roberts D, DN Veeramachaneni, WD Schlaff and CA Awoniyi. 2000. Effects of chronic dietary exposure to genistein, a phytoestrogen, during various stages of development on reproductive hormones and spermatogenesis in rats. Endocrine 13:281-286 https://doi.org/10.1385/ENDO:13:3:281
  56. Rossiter RC and AB Beck. 1966. Physiological and ecological studies on the estrogenic isoflavones in subterranean clover (Trifolium subterraneum) I. Effects of temperature. Aust. J. Agric. Res. 17:2937 https://doi.org/10.1071/AR9660029
  57. Rubanyi GM, A Johns and K Kauser. 2002. Effect of estrogen on endothelial function and angiogenesis. Vase. Pharmacol. 38:8998 https://doi.org/10.1016/S0306-3623(02)00131-3
  58. Schmitt E, L Lehmann, M Metzler and H Stopper. 2002. Hormonal and genotoxic activity of resveratrol. Toxicol. Lett. 136:133-142 https://doi.org/10.1016/S0378-4274(02)00290-4
  59. Sonee M, T Sum, C Wang and SK Mukherjee. 2004. The soy isoflavone, genistein, protects human cortical neuronal cells from oxidative stress. Neurotoxicology 25: 885-91 https://doi.org/10.1016/j.neuro.2003.11.001
  60. Stampfer M, W Willett, G Colditz, B Rosner, F Speizer and C Hennekens. 1985. A prospective study of postmenopausal estrogen therapy and coronary heart disease. N. Engl. J. Med. 313:1044-1049 https://doi.org/10.1056/NEJM198510243131703
  61. Srilatha Band PG Adaikan. 2004. Estrogen and phytoestrogen predispose to erectile dysfunction: do ERalpha and ER-beta in the cavernosum playa role? Urology 63:382-386 https://doi.org/10.1016/j.urology.2003.08.042
  62. Takeshita A, N Koibuchi, J aka, M Taguchi, Y Shishiba and Y Ozawa. 2001. Bisphenol-A, an environmental estrogen, activates the human orphan nuclear receptor, steroid and xenobiotic receptor-mediated transcription. Eur. J. Endocrinol. 145:513-517 https://doi.org/10.1530/eje.0.1450513
  63. Teede HJ, FS Dalais, D Kotsopoulos, Y- L Liang, S Davis and BP McGrath. 2001. Dietary soy has both beneficial and potentially adverse cardiovascular effects: a placebo-controlled study in men and postmenopausal women. J. Clin. Endocrinol. Metab. 86:3053-3060 https://doi.org/10.1210/jc.86.7.3053
  64. Thompson JN. 1999. The evolution of species interactions. Science 284:2116-2118 https://doi.org/10.1126/science.284.5423.2116
  65. Thornton JW, E Need and D Crews. 2003. Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling. Science 301:1714-1717 https://doi.org/10.1126/science.1086185
  66. Vastano BC, Y Chen, N Zhu, C-T Ho, Z Zhou and RT Rosen. 2000. Isolation and identification of stilbenes in two varieties of Polygonm cuspidatum. J. Agric. Food Chern. 48:253-256 https://doi.org/10.1021/jf9909196
  67. Wang D, J Gutkowska, M Marcinkiewicz, G Rachelska and M Jankowski. 2003. Genistein supplementation stimulates the oxytocin system in the aorta of ovariectomized rats. Cardiovasc. Res. 57:186-194 https://doi.org/10.1016/S0008-6363(02)00655-7
  68. Washburn S, GL Burke, T Morgan and M Anthony. 1999. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 6:7-13
  69. Wise PM. 2002. Estrogens and neuroprotection. Trends Endocrinol. Metab. 13:229-30 https://doi.org/10.1016/S1043-2760(02)00611-2
  70. Wynne-Edwards KE. 2001. Evolutionary biology of plant defenses against herbivory and their predictive implications for endocrine disruptor susceptibility in vertebrates. Environ. Health Perspect. 109:443-448
  71. Xu YJ, RD Traystman, P Hum and M Wang. 2003. Neuritelocalized estrogen receptora mediates rapid signaling by estrogen. J. Neurosci. Res. 74:1-11 https://doi.org/10.1002/jnr.10725