The need to decide if all estrogens are intrinsically similar.
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 17-beta-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.
Moggs
Jonathan G
JG
Syngenta CTL, Alderley Park, Cheshire SK10 4TJ, United Kingdom. jonathan.moggs@syngenta.com
Ashby
John
J
Tinwell
Helen
H
Lim
Fei Ling
FL
Moore
David J
DJ
Kimber
Ian
I
Orphanides
George
G
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D004054:Diethylstilbestrol / Q000009:adverse effects* / Q000494:pharmacology*; D004958:Estradiol / Q000009:adverse effects* / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D019833:Genistein / Q000009:adverse effects* / Q000494:pharmacology*; D049691:History, Medieval; D007529:Isoflavones / Q000009:adverse effects* / Q000494:pharmacology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D048789:Phytoestrogens; D028321:Plant Preparations / Q000009:adverse effects* / Q000494:pharmacology*; D018570:Risk Assessment; D015854:Up-Regulation; D014599:Uterus / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D004958:Estradiol; D004054:Diethylstilbestrol; D019833:Genistein