In vitro test systems for the evaluation of the estrogenic activity of natural products

Many compounds of plant origin with the ability to bind to the estrogen receptor have been identified in the last decades. There is evidence that the consumption of some of these phytoestrogens may have beneficial effects but it also seems possible that others may act as endocrine disrupters. For this reason there is a need to characterise the estrogenic potency of these substances. In vitro test systems offer the possibility to screen compounds very efficiently. Routinely in use and widespread for the determination of estrogenicity are: (I) receptor binding assays, (II) cell-proliferation assays (E-screens), (III) reporter gene assays, and (IV) the analysis of the regulation of endogenous estrogen sensitive genes in cell lines. The basis of all these test systems are molecular mechanisms which are involved in the classical estrogen action. In addition, in the last years several test systems for the investigation of non-classical estrogenic effects have been established. An example for such an effect is the modulation of the expression of interleukin-6, a cytokine that appears to be a key molecule in the osteoporotic process, by estrogens. Summarising the advantages and the issues of all presented in vitro test systems, it seems to be evident that only the analysis of results obtained in a combination of several in vitro test systems may validly predict effects in vivo.