The differential ability of the phytoestrogen genistein and of estradiol to induce uterine weight and proliferation in the rat is associated with a substance specific modulation of uterine gene expression

In this study the ability of the phytoestrogen genistein (GEN) to regulate proliferation in the rat uterine tissue and the associated molecular mechanisms were investigated in a dose and time dependent manner. A single administration of GEN induced a rapid increase of the uterine weight during the first 24 h. In contrast to E2, treatment with GEN for 3 days did not result in a further increase of the uterine weight. GEN only marginally effected the thickness of the uterine epithelium and the expression of epithelial proliferating cell nuclear antigen (PCNA). Whereas, estrogen sensitive genes were modulated significantly, the expression of key genes involved in the regulation of proliferation (PCNA, ERalpha/ERbeta ratio) remained unaffected by GEN. Our results indicate that GEN has only a limited ability to activate molecular mechanisms involved in the induction of proliferation whereas estrogen sensitive genes are induced in a estrogen like manner. (C) 2004 Elsevier Ireland Ltd. All rights reserved.