Endocrine Abstracts

Phytoestrogens (PEs) have a weak affinity for the oestrogen receptor. There is, however, no consistent evidence that, on a normal diet, circulating levels of PEs reach sufficient concentrations to exert significant oestrogenic/anti-oestrogenic effects. Phytoestrogens have been implicated in other cellular actions, not all of which necessarily involve the oestrogen receptor. Studies on cell-free systems and cell lines have demonstrated dose-dependent inhibitory effects of PEs on the activitiy of key steroidogenic enzymes and some studies have suggested this is due to competitive inhibition with respective steroid substrates. We have been investigating the effects of PEs on aromatase and 3 beta- and 17beta-hydroxysteroid dehydrogenases (HSDs) in primary cultures of human granulosa luteal (GL) cells. Our recent work has looked at the effects of PEs on the expression of key steroidogenic enzymes and whether such effects may be mediated by the ability of some PEs to inhibit cell signaling pathways.

The presentation will compare the inhibitory effects of different phytoestrogens on steroidogenic enzyme activity observed in cell-free preparations, cell lines and human GL cells and show that different experimental models produce different results. Our latest data on the effects of phytoestrogens on enzyme expression and cell signalling pathways in GL cells will also be presented as will our data on the effects of mixtures of phytoestrogens that would occur in vivo. The paradox that phytoestrogens are promoted as natural alternatives to HRT (oestrogenic?) and yet epidemiological evidence suggests they may protect against hormone- dependent breast and prostate cancer (inhibitors of local steroid production?) needs to be resolved.