Pharmacologic, but not dietary, genistein supports endometriosis in a rat model.
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.
Cotroneo
M S
MS
Department of Pharmacology and Toxicology and the Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Lamartiniere
C A
CA
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004195:Disease Models, Animal; D004343:Drug Implants; D004715:Endometriosis / Q000139:chemically induced* / Q000473:pathology / Q000601:surgery; D004958:Estradiol / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D004970:Estrone / Q000032:analysis / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D013058:Mass Spectrometry; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000032:analysis / Q000097:blood; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D004343:Drug Implants; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004970:Estrone; D011374:Progesterone; D004958:Estradiol; D019833:Genistein