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Estrogenic Activities in Rodent Estrogen-Free Diets

Department of Pharmacological Sciences (P.C., A.B., P.S., A.M.), Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy; Third Laboratory/Biotechnology (E.B., D.D.L.), Civic Hospital of Brescia, University of Brescia, 25123 Brescia, Italy

Address all correspondence and requests for reprints to: Adriana Maggi, Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. E-mail: adriana.maggi{at}unimi.it.

Diets lacking soy and - derivatives that are considered to be estrogen-free by standard bioassays (uterotrophic assay and vaginal opening) have been revealed to contain considerable amounts of compounds able to transcriptionally activate the estrogen receptors (ERs) and stimulate luciferase expression in several organs of the ERE-Luc reporter mouse. By molecular imaging, we show that ER activation is present in nonreproductive organs to an extent similar to that observed with the administration of 17ß-estradiol, and it is not influenced by orchiectomy or treatment with an aromatase inhibitor. This, together with the use of a completely synthetic diet, proves that the activation of ERs observed is due to estrogenic compounds present in commercial diets and that it is not a secondary event determined by food consumption and metabolism. The pervasiveness of estrogenic compounds in nature poses the question of how relevant and necessary is the daily ingestion of natural compounds active through the ERs for the maintenance of a correct metabolism in both male and female mammals.

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