Early estrogen exposure leads to later prostate c...( o demonstrate that early estrogen or BP...),Health

o demonstrate that early estrogen or BPA exposure permanently changed the methylation, or tagging, of specific stretches of DNA in the neonate's prostate cells, a phenomenon referred to as epigenetic reprogramming. In epigenetic reprogramming, gene expression is altered without changing DNA sequences or content. Several of the epigenetically altered sites turned out to be in important genes that regulate cellular functions.

The researchers conclude that exposure to environmental estrogens, such as BPA, or natural estrogens affect the pattern of gene expression in the prostate during development, and in so doing promote prostate disease with aging.

One of the altered genes, phosphodiesterase 4 (PDE4D4), was examined in greater detail. The researchers found that the methylation of PDE4D4 can permanently change its pattern of expression in the prostate. This gene should normally shut down in adult life, but after early exposure to estradiol or BPA, the exposed animals' prostates continued to express it at high levels. Similar high levels due to methylation of the gene were found in prostate cancer cells but not in normal cell lines.

Because the methylation marks of epigenetic reprogramming were found before any disease was observed, the methylation may be useful as a way to identify men at higher prostate disease risk, Prins said, which may have resulted from early exposure to endocrine disruptors.

"These findings are true for an animal model, and application to human prostate disease will await future studies," the authors concluded. Ho is first author of the study and professor and chairman of environmental health at the University of Cincinnati.

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Contact: Jeanne Galatzer-Levy
jgala@uic.edu
312-996-1583
University of Illinois at Chicago
1-Jun-2006

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