Cross-species and interassay comparisons of phytoestrogen action.

Abstract

This paper compiles animal and human data on the biologic effects and exposure levels of phytoestrogens in order to identify areas of research in which direct species comparisons can be made. In vitro and in vivo assays of phytoestrogen action and potency are reviewed and compared to actions, dose-response relationships, and estimates of exposure in human subjects. Binding studies show that the isoflavonoid phytoestrogens are high-affinity ligands for estrogen receptors (ERs), especially ER beta, but have lower potency in whole-cell assays, perhaps because of interactions with binding proteins. Many other enzymatic actions require concentrations higher than those normally seen in plasma. In vivo data show that phytoestrogens have a wide range of biologic effects at doses and plasma concentrations seen with normal human diets. Significant in vivoresponses have been observed in animal and human tests for bone, breast, ovary, pituitary, vasculature, prostate, and serum lipids. The doses reported to be biologically active in humans (0.4--10 mg/kg body weight/day) are lower than the doses generally reported to be active in rodents (10--100 mg/kg body weight/day), although some studies have reported rodent responses at lower doses. However, available estimates of bioavailability and peak plasma levels in rodents and humans are more similar. Steroidogenesis and the hypothalamic-pituitary-gonadal axis appear to be important loci of phytoestrogen actions, but these inferences must be tentative because good dose-response data are not available for many end points. The similarity of reported proliferative and antiproliferative doses illustrates the need for fuller examination of dose-response relationships and multiple end points in assessing phytoestrogen actions.

Urinary and serum concentrations of seven phytoestrogens in a human reference population subset

“…For matairesinol and equol, nondetectable concentrations were obtained for most of the serum samples. Detectable levels of equol in serum have been reported in previous studies, but the reported values were below our method's limit of detection (Adlercreutz et al, 1993;Whitten and Patisaul, 2001). Time of collection of the blood sample is an important variable for the determination of phytoestrogens because of their short halflives (King and Bursill, 1998).…”

Time dependency of uterine effects of naringenin type phytoestrogens in vivo

“…Their function is estrogen-like, but in contrast to the natural ligand estradiol they act in an organ selective and gene specific way . The estrogenic effects of specific phytoestrogens have been characterized to different degrees (Whitten and Patisaul, 2001). …”

The phytoestrogen genistein induces thymic and immune changes: A human health concern?

“…However, estrogenicity of genistein is only 1͞1,000th to 1͞10,000th that of E 2 (7). In addition, only a small fraction of circulating genistein or daidzein is the active aglycone.…”

“…Work on estrogenic effects of phytoestrogens has focused on reproductive organs (7). However, thymus expresses both estrogen receptor (ER) ␣ and ER␤, and estrogen treatment of developing rodents induces thymic atrophy and immune suppression (8,9).…”