Pharmacologic, but not dietary, genistein supports endometriosis in a rat model

Endometriosis is a disease in which uterine tissue proliferates in extraute rine sites. Using a surgical model to simulate endometriosis, we explored t he potential for the phytoestrogen genistein, by injection and diet, to sus tain endometriosis in rats. Uterine tissue was attached to intestinal mesen tery of 8-week-old Sprague Dawley rats. After 3 weeks, the rats were ovarie ctomized and the implants measured. Following 3 weeks of daily injections o r exposure to dietary genistein, animals were necropsied and implants locat ed and measured. Injections of genistein (50 and 16.6 mug/g BW) or estrone (1 mug/rat) sustained the implants; injection of sesame oil (vehicle for es trone), dimethylsulfoxide (DMSO; vehicle for genistein), or genistein at 5. 0 mug/g BW did not sustain implants. Dietary genistein (250 or 1000 mg geni stein/kg AIN-76A diet) did not support the implants. In ovary-intact rats e xposed to 250 mg genistein/kg AIN-76A diet, implant size was not altered, c ompared to control-fed animals, To assess estrogenic actions of genistein, we measured uterine estrogen receptor alpha (ER-LU) and progesterone recept or (PR) isoforms A and B be Western blot analyses. Injections of estrone or genistein (50 or 16.6 mug/g BW) significantly reduced uterine ER-ru compar ed to vehicle-treated animals. PR (B) was significantly increased by all in jected doses of genistein or estrone and by the higher dietary dose (1000 m g genistein/kg AIN-76A). PR (A) was significantly increased by injected dos es of genistein (16.6 and 5.0 mug/g BW). We conclude that pharmacologic inj ections, but not dietary physiological concentrations of genistein, support surgically induced endometriosis in rats. Our results suggest a critical r ole for ER modulation and genistein bioavailability in the maintenance of t he implants.