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

Michelle S. Cotroneo, M S Cotroneo, C A Lamartiniere
Toxicological sciences : an official journal of the Society of Toxicology · 2001 · vol. 61(1) , pp. 68–75 · doi:10.1093/toxsci/61.1.68 · PMID:11294976 · W2099390148
article OA: bronze CC0 ⤵ 27 in-corpus citations
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Pharmacologic genistein injections, but not dietary genistein, supported endometriosis implants in a rat model by modulating estrogen and progesterone receptor expression.

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Abstract

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 microg/g BW) or estrone (1 microg/rat) sustained the implants; injection of sesame oil (vehicle for estrone), dimethylsulfoxide (DMSO; vehicle for genistein), or genistein at 5.0 microg/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-alpha) and progesterone receptor (PR) isoforms A and B by Western blot analyses. Injections of estrone or genistein (50 or 16.6 microg/g BW) significantly reduced uterine ER-alpha 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 microg/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.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Diet Disease Models, Animal Drug Implants Endometriosis Estrone Genistein Receptors, Estrogen Receptors, Estrogen Receptors, Progesterone Receptors, Progesterone Uterus Animals Blotting, Western Body Weight Body Weight Chromatography, High Pressure Liquid Endometriosis Endometriosis Endometriosis Estradiol

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References (48)

Cited by (27)

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