Journal Article

Pharmacologic, but Not Dietary, Genistein Supports Endometriosis in a Rat Model

Michelle S. Cotroneo and Coral A. Lamartiniere

in Toxicological Sciences

Volume 61, issue 1, pages 68-75
Published in print May 2001 | ISSN: 1096-6080
Published online May 2001 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/61.1.68
Pharmacologic, but Not Dietary, Genistein Supports Endometriosis in a Rat Model

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Endometriosis is a disease in which uterine tissue proliferates in extrauterine sites. Using a surgical model to simulate endometriosis, we explored the potential for the phytoestrogen genistein, by injection and diet, to sustain endometriosis in rats. Uterine tissue was attached to intestinal mesentery of 8-week-old Sprague Dawley rats. After 3 weeks, the rats were ovariectomized and the implants measured. Following 3 weeks of daily injections or exposure to dietary genistein, animals were necropsied and implants located and measured. Injections of genistein (50 and 16.6 μg/g BW) or estrone (1 μg/rat) sustained the implants; injection of sesame oil (vehicle for estrone), dimethylsulfoxide (DMSO; vehicle for genistein), or genistein at 5.0 μg/g BW did not sustain implants. Dietary genistein (250 or 1000 mg genistein/kg AIN-76A diet) did not support the implants. In ovary-intact rats exposed to 250 mg genistein/kg AIN-76A diet, implant size was not altered, compared to control-fed animals. To assess estrogenic actions of genistein, we measured uterine estrogen receptor alpha (ER-α) and progesterone receptor (PR) isoforms A and B by Western blot analyses. Injections of estrone or genistein (50 or 16.6 μg/g BW) significantly reduced uterine ER-α compared to vehicle-treated animals. PR (B) was significantly increased by all injected doses of genistein or estrone and by the higher dietary dose (1000 mg genistein/kg AIN-76A). PR (A) was significantly increased by injected doses of genistein (16.6 and 5.0 μg/g BW). We conclude that pharmacologic injections, but not dietary physiological concentrations of genistein, support surgically induced endometriosis in rats. Our results suggest a critical role for ER modulation and genistein bioavailability in the maintenance of the implants.

Keywords: genistein; endometriosis; estrogen-; progesterone-receptors; uterus; rat

Journal Article.  5844 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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