Editors' ChoiceSteroids

Physiological Effects of Dietary Phytoestrogens

STKE  19 Jul 2005:
Vol. 2005, Issue 293, pp. tw264
DOI: 10.1126/stke.2932005tw264

In the mouse, the coordinated effects of ovarian estrogen (estradiol-17β, E2) and progesterone (P4) regulate uterine cell proliferation and differentiation, thereby determining the timing of uterine receptivity for blastocyst implantation. After relocation of their research program, Wang et al. noted variability in responses to ovarian hormones and undertook an investigation of the role of diet-derived phytoestrogens in modulating the uterine response to endogenous steroid hormones. Mice were fed with one of two brands of mouse chow with similar composition but different isoflavone content, 5V00 [less than 50 parts per million (ppm) isoflavones] or 5001 (more than 400 ppm isoflavones). When maintained on these diets for 8 weeks and ovariectomized 2 weeks before sacrifice, mice on the 5001 diet had higher uterine weight compared with 5V00 mice, exhibited bromodeoxyuridine incorporation into uterine epithelial cells, and showed an enhanced response (increased uterine weight) to treatment with E2 or P4. The authors used reverse transcription polymerase chain reaction (RT-PCR) to show that 5001 mice had increased abundance of mRNAs encoding the estrogen target genes PR (nuclear progesterone receptor), LF (lactoferrin), and LIF (leukemia inhibitory factor) and decreased abundance of ERα (nuclear estrogen receptor α) and sFRP2 (secreted frizzled related protein 2). Consistent with this, immunohistochemical analysis indicated that 5001 mice had increased PR abundance and decreased ERα abundance compared with the 5V00 mice. Finally, the authors observed that the temporal window during which blastocyst implantation occurred was advanced by about 4 hours in nonovariectomized mice fed the high-phytoestrogen diet. Thus, the authors conclude that, at least in mice, dietary phytoestrogens can modulate the response to endogenous hormones and influence their physiological effects.

H. Wang, S. Tranguch, H. Xie, G. Hanley, S. K. Das, S. K. Dey, Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus. Proc. Natl. Acad. Sci. U.S.A. 102, 9960-9965 (2005). [Abstract] [Full Text]