| The Need to Decide If All Estrogens Are Intrinsically Similar Jonathan G. Moggs, John Ashby, Helen Tinwell, Fei Ling Lim, David J. Moore, Ian Kimber, and George Orphanides Syngenta CTL, Alderley Park, Cheshire, United Kingdom Abstract We used gene expression profiling to investigate whether the molecular effects induced by estrogens of different provenance are intrinsically similar. In this article we show that the physiologic estrogen 17ß-estradiol, the phytoestrogen genistein, and the synthetic estrogen diethylstilbestrol alter the expression of the same 179 genes in the intact immature mouse uterus under conditions where each chemical has produced an equivalent gravimetric and histologic uterotrophic effect, using the standard 3-day assay protocol. Data are also presented indicating the limitations associated with comparison of gene expression profiles for different chemicals at times before the uterotrophic effects are fully realized. We conclude that the case has yet to be made for regarding synthetic estrogens as presenting a unique human hazard compared with phytoestrogens and physiologic estrogens. Key words: diethylstilbestrol, estrogen, gene expression, genistein, microarray, phytoestrogen, toxicogenomics, uterus. Environ Health Perspect 112:1137-1142 (2004) . doi:10.1289/ehp.7028 available via http://dx.doi.org/ [Online 19 May 2004] Address correspondence to J.G. Moggs, Syngenta CTL, Alderley Park, Cheshire, SK10 4TJ UK. Telephone: 44-1625-519315. Fax: 44-1625-585715. E-mail: jonathan.moggs@syngenta.com We thank A. Soames for the histopathology data, I. Kupershmidt and E. Hunter (Silicon Genetics) for advice on statistical analysis of microarray data, and T. Barlow (Food Standards Agency) for critical comments. This work was partially supported by the U.K. Food Standards Agency. The authors declare they have no competing financial interests. Received 12 February 2004 ; accepted 19 May 2004. The full version of this article is available for free in HTML or PDF formats. |