{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:44:26Z","timestamp":1786632266748,"version":"build-2736575974"},"reference-count":49,"publisher":"American Chemical Society (ACS)","issue":"Suppl 1","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":3857,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The isoflavone genistein (GEN) is found in soy (Glycine max) and red clover (Trifolium pratense). The estrogenic activity of GEN is known, and it is widely advertised as a phytoestrogen useful in alleviating climacteric complaints and other postmenopausal disorders. Knowledge of effects of long-term administration of GEN in laboratory animals is scarce, and effects in the uterus and mammary gland after long-term administration have not been studied. The uterus and mammary gland are known to be negatively influenced by estrogens used in hormone therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We administered two doses of GEN [mean daily uptake 5.4 (low) or 54 mg\/kg (high) body weight (bw)] orally over a period of 3 months to ovariectomized (ovx) rats and compared the effects with a treatment with two doses of 17\u03b2-estradiol [E2; 0.17 (low) or 0.7 mg\/kg bw (high)]. Mammary glands, vaginae, and uteri were investigated morphologically and immunohistochemically. We quantified the expression of proliferating cell nuclear antigen (PCNA) and progesterone receptor (PR) in the mammary gland.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In rats treated with either of the E2 doses or the high GEN dose, we found increased uterine weight, and histologic analysis showed estrogen-induced features in the uteri. In vaginae, either E2 dose or GEN high induced hyperplastic epithelium compared with the atrophic controls. In the mammary gland, E2 (either dose) or GEN increased proliferation and PR expression. Serum levels of luteinizing hormone were decreased by E2 (both doses) but not by GEN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In summary, E2 and GEN share many effects in the studied organs, particularly in the vagina, uterus, and mammary gland but not in the hypothalamo\/pituitary unit.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1289\/ehp.9367","type":"journal-article","created":{"date-parts":[[2007,6,4]],"date-time":"2007-06-04T12:51:31Z","timestamp":1180961491000},"page":"62-68","source":"Crossref","is-referenced-by-count":52,"title":["Effects of Chronic Genistein Treatment in Mammary Gland, Uterus, and Vagina"],"prefix":"10.1021","volume":"115","author":[{"given":"Guillermo","family":"Rimoldi","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Endocrinology, Georg-August-University, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Christoffel","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Endocrinology, Georg-August-University, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Seidlova-Wuttke","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Endocrinology, Georg-August-University, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubertus","family":"Jarry","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Endocrinology, Georg-August-University, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Wuttke","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Endocrinology, Georg-August-University, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2007,6,8]]},"reference":[{"issue":"3","key":"2026080413024036400_micit1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1080\/13697130500117946","article-title":"Urogenital effects of selective estrogen receptor modulators: a systematic review","volume":"8","author":"Albertazzi","year":"2005","journal-title":"Climacteric"},{"issue":"2","key":"2026080413024036400_micit2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/carcin\/bgg198","article-title":"Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats","volume":"25","author":"Allred","year":"2004","journal-title":"Carcinogenesis"},{"issue":"1471","key":"2026080413024036400_micit3","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1098\/rstb.2006.1860","article-title":"Modulation of appetite by gonadal steroid hormones","volume":"361","author":"Asarian","year":"2006","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"9382","key":"2026080413024036400_micit4","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S0140-6736(03)14065-2","article-title":"Breast cancer and hormone-replacement therapy in the Million Women Study","volume":"362","author":"Beral","year":"2003","journal-title":"Lancet"},{"issue":"8","key":"2026080413024036400_micit5","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1021\/jf021114s","article-title":"Evaluation of the estrogenic effects of legume extracts containing phytoestrogens","volume":"51","author":"Boue","year":"2003","journal-title":"J Agric Food Chem"},{"issue":"3","key":"2026080413024036400_micit6","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jsbmb.2004.03.118","article-title":"Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types","volume":"91","author":"Bovee","year":"2004","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"suppl 1","key":"2026080413024036400_micit7","first-page":"11","article-title":"Hormone replacement therapy in the post-Women\u2019s Health Initiative era. 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