Effects of nutrition relevant mixtures of phytoestrogens on steroidogenesis, aromatase, estrogen, and androgen activity.
Phytoestrogens (PEs) are naturally occurring plant components produced in a large range of plants. They can induce biologic responses in vertebrates by mimicking or modulating the action or production of endogenous hormones. This study examined mixtures of 12 food relevant PEs for effects on steroid hormone production, aromatase activity, estrogenic activity, and for interaction with the androgen receptor. The results show that a mixture of all tested PEs increased estradiol production and decreased testosterone production in H295R human adrenal corticocarcinoma cells, indicating an induced aromatase activity. Furthermore, exposure of the H295R cells to isoflavonoids caused a decrease in testosterone production, and various mixtures of PEs significantly stimulated MCF-7 human breast adenocarcinoma cell growth and induced aromatase activity in JEG-3 choriocarcinoma cells. The estrogenic effect in the MCF7 cells of the isoflavonoid mixture and coumestrol was supported by an observed increase in progesterone receptor protein expression as well as a decreased ERalpha expression. Overall, the results support that nutrition-relevant concentrations of PEs both alone and in mixtures possess various endocrine disrupting effects, all of which need to be considered when assessing the effects on human health.
Taxvig
Camilla
C
National Food Institute, Technical University of Denmark, Department of Toxicology and Risk Assessment, Søborg, Denmark. camta@food.dtu.dk
Elleby
Anders
A
Sonne-Hansen
Katrine
K
Bonefeld-Jørgensen
Eva C
EC
Vinggaard
Anne Marie
AM
Lykkesfeldt
Anne E
AE
Nellemann
Christine
C
D000306:Adrenal Cortex Neoplasms; D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004958:Estradiol / Q000096:biosynthesis; D047628:Estrogen Receptor alpha / Q000032:analysis; D004967:Estrogens / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D005502:Food; D006801:Humans; D048789:Phytoestrogens / Q000008:administration & dosage*; D010945:Plants, Edible / Q000737:chemistry; D011944:Receptors, Androgen / Q000187:drug effects* / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis; D013256:Steroids / Q000096:biosynthesis*; D013739:Testosterone / Q000096:biosynthesis
D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D004967:Estrogens; D005419:Flavonoids; D048789:Phytoestrogens; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D013256:Steroids; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase