Structural Features of Alkylphenolic Chemicals Associated with Estrogenic Activity

doi:10.1074/jbc.272.6.3280

Structural Features of Alkylphenolic Chemicals Associated with Estrogenic Activity*

From the Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex UB8 3PH, United Kingdom

^‡ To whom correspondence should be addressed. Tel.: 01895-274-000; Fax: 01895-274-348.

Abstract

The ability of certain man-made chemicals to mimic the effects of natural steroid hormones and their potential to disrupt the delicate balance of the endocrine system in animals are of increasing concern. The growing list of reported hormone-mimics includes the alkylphenolic (AP) compounds, a small number of which have been reported to be weakly estrogenic. In their most basic form, APs are composed of an alkyl group, which can vary in size, branching, and position, joined to a phenolic ring. The aim of this project was to identify the important structural features responsible for the estrogenic activity of AP chemicals. This was achieved by incubating APs with different structural features in a medium containing a previously described estrogen-inducible strain of yeast (Saccharomyces cerevisiae) expressing the human estrogen receptor and comparing their activity spectrophotometrically by the resulting color change of the medium. The results were compared to the effects of the main natural estrogen 17β-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 composed of between 6 and 8 carbons located at the para position on an otherwise unhindered phenol ring. The results are discussed in relation to the purity and composition of the chemicals tested.

Footnotes

↵* This work was funded by the Environmental Agency (National Research and Development Project 490). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

CPRG

chlorophenol red-β-D-galactopyranoside

AP

alkylphenolic

APE

ethoxylated alkylphenolic compound.
↵² E. J. Routledge and J. P. Sumpter, unpublished result.
↵³ C. Green, personal communication.
- Received July 15, 1996.
- Revision received October 15, 1996.