Phytoestrogens and Mycoestrogens Bind to the Rat Uterine Estrogen Receptor

Abstract

Consumption of phytoestrogens and mycoestrogens in food products or as dietary supplements is of interest because of both the potential beneficial and adverse effects of these compounds in estrogen-responsive target tissues. Although the hazards of exposure to potent estrogens such as diethylstilbestrol in developing male and female reproductive tracts are well characterized, less is known about the effects of weaker estrogens including phytoestrogens. With some exceptions, ligand binding to the estrogen receptor (ER) predicts uterotrophic activity. Using a well-established and rigorously validated ER-ligand binding assay, we assessed the relative binding affinity (RBA) for 46 chemicals from several chemical structure classes of potential phytoestrogens and mycoestrogens. Although none of the test compounds bound to ER with the affinity of the standard, 17beta-estradiol (E(2)), ER binding was found among all classes of chemical structures (flavones, isoflavones, flavanones, coumarins, chalcones and mycoestrogens). Estrogen receptor relative binding affinities were distributed across a wide range (from approximately 43 to 0.00008; E(2) = 100). These data can be utilized before animal testing to rank order estimates of the potential for in vivo estrogenic activity of a wide range of untested plant chemicals (as well as other chemicals) based on ER binding.

The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies.

“…Four other laboratories, which either participated in phase 1 (Kanno et al 2001) or the coded single-dose studies in phase 2 (Kanno et al 2003), did Blair et al (2000) and Branham et al (2002). b The binding curves were generated in a single laboratory on the basis of a single protocol using closely interspersed concentrations and performed in triplicate.…”

“…These data are compliant with test substance selection recommendations to demonstrate the characteristics of a bioassay for validation studies and the relationship of a bioassay to other assays in a hierarchical, tiered approach (ICCVAM 1997;OECD 1998b). The chemical identities and estrogenreceptor binding data from Blair et al (2000) and Branham et al (2002) are shown in Table 1. The binding affinities of the selected weak agonists relative to 17β-estradiol cover a range of almost three orders of magnitude, for example, log -0.35 to -3.20, and even the two most potent selected agonists, GN and the metabolite of MX, are almost three orders of magnitude weaker than the reference EE agonist.…”

Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus

“…There is evidence that phytoestrogens bind ERs and modulate a variety of estrogen-dependent processes (35,36). It is also possible that diets with higher phytoestrogen levels exert their estrogenic activity by regulating ER␣ and PR expression, which then affects uterine responsiveness to estrogen and P 4 .…”

Urinary phytoestrogens and cancer, cardiovascular, and all-cause mortality in the continuous National Health and Nutrition Examination Survey

“…Phytoestrogens can induce biologic responses due to their structural similarity to 17β-estradiol when they are consumed in the diet [16]. The biologic responses from phytoestrogens include estrogenic, anti-estrogenic, anti-oxidative, anti-viral, anti-bacterial, and antiproliferative effects [11].…”