Effects of phytoestrogen extracts isolated from flax on hormone

Aim and setting: To test the effects of crude extracts from flax (Linum usitatissimum) on progesterone and estradiol and ERα and β/PR production in choriocarcinoma cell lines Jeg 3 and BeWo. Tumor trophoblast cells (Jeg 3 and BeWo) were incubated in the presence of different concentrations of the flax crude extracts. Estradiol and progesterone production was measured. Estrogen receptor α and β as well as progesterone receptor expressions were also assessed.   Results: In Jeg 3 cells, progesterone production was downregulated by flax root and leaves extract, while in BeWo cells only flax root extract did manage to downregulate progesterone production. ERβ expression was significantly downregulated by flax root and flax leaves extract in both cell lines; on the contrary, ERα expression was increased by flax leaves extract in BeWo cells. PR expression was downregulated by flax leaves extract in Jeg 3 and by flax root extract in BeWo cells.  Conclusion: Flax extracts derived from leaves and especially from roots can modify progesterone and possibly estradiol production, while at the same time they seem to alter ERβ expression. Further studies on animal models and adequately designed retrospective epidemiological studies are imperative to clarify this role upon progesterone (Authors abstract).
The mammalian lignans enterolactone and enterodiol, mostly found in human plasma and urine, are formed by the conversion of dietary precursors such as secoisolariciresinol and matairesinol by the colonic microflora. A substantial number of in vitro cell culture studies and in vivo animal experiments have also shown that phytoestrogens are able to inhibit tumour growth as well as cancer invasiveness and metastasis. Since the flax plant is considered a source of phytoestrogens, the aim of this study was to test the effect of crude extracts from flax roots, stems and leaves on estradiol and progesterone production as well as on the expression of estrogen- and progesterone receptors in Jeg 3 and BeWo tumour trophoblast cells. The stereoidogenic capabilities of choriocarcinoma cells in culture are similar to those of the in vivo placenta and support their use as an experimental model of placental steroidogenesis. The MS analysis revealed that the flax root extract contains both isoflavones and lignans in their free chemical form, whereas in stem and leaves phytoestrogens are bound to glycosides or form dimers. Taking into consideration that phytoestrogens are mostly effective in their free form, it could be justified why the root extract had the most significant effect on both Jeg 3 and BeWo cells. The stem extract had no effect on both cell lines implying that the phytoestrogenic consistence of the flax stem can be either of low concentration or has phytoestrogens in chemical forms that would need further processing− as this is done for example by the intestinal flora and in the liver− to release the relevant free forms. Of note as well, is the significant increase of progesterone production found in Jeg 3 cells by the low concentration of the flax leaves extract; this could imply a bi-phasic role of flax leaves phytoestrogenic component. The current data have shown that flax root extract in moderate to high concentrations can decrease estradiol production by Jeg 3. In conclusion, the current study demonstrates that flax extracts derived from leaves and especially from roots can modify progesterone and possibly estradiol production, while at the same time they seem to alter ERβ expression. Flax consumption can implicate early pregnancy outcome since progesterone is crucial to implantation and early pregnancy maintenance. Further studies on animal models and adequately designed retrospective epidemiological studies are imperative to clarify this role upon progesterone production (Editors comments)