Genistein - an agent of endocrine disruptive effects and relief of menopausal disorders – University of Copenhagen

NaToxAq > Toxin of the week > Genistein

12 March 2018

Genistein - an agent of endocrine disruptive effects and relief of menopausal disorders

Natural toxin

Phytoestrogens can have both positive and negative effects.

Depending on your age, sex and occupation, you may have different associations with the term 'phytoestrogen'. For the young environmental or health scientist, it may be associated with endocrine disruptive effects; while for the middle-aged female, it may signify relief from menopausal disorders.

Phytoestrogens are non-steroidal compounds naturally produced by plants that have the ability to elicit weak estrogenic or anti-estrogenic effects by interacting with endocrine receptors due to the similarity of the compounds to 17β-estradiol. There are four main compound categories causing phytoestrogenic effects: flavonoids, lignans, coumestans and stilbenes. The flavonoids is one of the largest and most studied groups with more than 10,000 compounds, and can be further divided into six subclasses: flavonols, flavones, flavanones, flavanols, anthrocyanins and isoflavones. The function of the flavonoids in the plants is thought to be protection against ultraviolet irradiation and defense against pathogens and insect pests. Phytoestrogens are found in many different plants, mainly legumes.

Genistein is one of the most well-known phytoestrogens. It is especially characteristic of soy beans, but can also be found in smaller amounts in e.g. red clover. It has further been detected in the aqueous environment in relation to agricultural activity and waste water. In soy, it is predominantly found as the inactive glycoside genistin, which can be hydrolyzed by acid and β-glycosidase in the human gut or environment to yield genistein. It belongs to the compound class isoflavones due to the 3-phenyl-1-benzopyran-4-one backbone; the specific location of the phenyl group distinguishes the isoflavones from the flavones.

Figure: structure of genistein, genistin and 17β-estradiol (OBS: only example pictures). Press image for interactive 3D model of genistein.

Besides its role in hormonal regulation, genistein has been shown to have positive effects in relation to osteoporosis, cardiovascular diseases and as an antioxidant, while its role in breast cancer prevention is debatable. The potential endocrine disruptive effects include malformations in the ovary, uterus and prostate, early puberty, reduced fertility and reproductive tract cancers. Especially infants appear at risk when fed soy formula as a replacement for breastfeeding.

SMILES: Oc1ccc(cc1)C\3=C\Oc2cc(O)cc(O)c2C/3=O

References:

  • Beck, V., Rohr. U., Jungbauer, A. (2005): Phytoestrogens derived from red clover: An alternative to estrogen replacement therapy? Journal of Steroid Biochemistry & Molecular Biology (94) 499-518.
  • Clotfelter, E.D., Rodriguez, A.C. (2006): Behavioural changes in fish exposed to phytoestrogens. Environmental Pollution 144, 833-839.
  • Hörger, C.C., Wettstein, F.E., Hungerbuehler, K., Bucheli, T.D. (2009): Occurrence and Origin of Estrogenic Isoflavones in Swiss River Waters. Environmental Science and Technology 43, 6151-6157.
  • König, M., Escher, B.I., Neale, P.A., Krauss, M., Hilscherová, K., Novák, J., Teodorović, I., Schulze, T., Seidensticker, S., Kamal Hashmi, M.A., Ahlheim, J., Brack, W. (2017) Impact of untreated wastewater on a major European river evaluated with a combination of in vitro bioassays and chemical analysis. Environmental Pollution 220, 1220-1230.
  • Morissette, M., Litim, N., Di Paolo, T. (2018): Natural Phytoestrogens: A class of Promising Neuroprotective Agents for Parkinson Disease. In: Discovery and Development of Neuroprotective Agents from Natural Products [Book, ed. Brahmachari, G., Publisher: J. Fedor, Elsevier Inc., p. 9-61.]
  • Moutsatsou, P. (2007): The spectrum of phytoestrogens in nature: our knowledge is expanding. Hormones 6(3) 173-193.
  • Mukund, V. Mukund, D., Sharma, V., Mannarapu, M., Alam. A. (2018): Genistein: Its role in metabolic diseases and cancer.
  • Patisaul, H.B. and Jefferson, W. (2010): The pros and cons of phytoestrogens. Frontiers in neuroendocrinology 31(4), 400-419.

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