STRUCTURAL FEATURES OF ALKYLPHENOLIC CHEMICALS ASSOCIATED WITH ESTROGENIC ACTIVITY

The ability of certain man-made chemicals to mimic the effects of natu ral steroid hormones and their potential to disrupt the delicate balan ce of the endocrine system in animals are of increasing concern, The g rowing list of reported hormone-mimics includes the alkylphenolic (AP) compounds, a small number of which have been reported to be weakly es trogenic, in their most basic form, APs are composed of an alkyl group , which can vary in size, branching, and position, joined to a phenoli c ring, The aim of this project was to identify the important structur al features responsible for the estrogenic activity of AP chemicals, T his was achieved by incubating APs with different structural features in a medium containing a previously described estrogen-inducible strai n of yeast (Saccharomyces cerevisiae) expressing the human estrogen re ceptor and comparing their activity spectrophotometrically by the resu lting color change of the medium. The results were compared to the eff ects of the main natural estrogen 17 beta-estradiol. The data indicate that both the position (para > meta > ortho) and branching (tertiary > secondary = normal) of the alkyl group affect estrogenicity. Optimal estrogenic activity requires a single tertiary branched alkyl group c omposed of between 6 and 8 carbons located at the pam position on an o therwise unhindered phenol ring. The results are discussed in relation to the purity and composition of the chemicals tested.