title: Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats.
abstract: There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P<0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genes than E2 at 152 genes (P<0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P<0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens.
authors.affiliation: Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States. Electronic address: mronis@lsuhsc.edu.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Ronis
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
authors.forename: Horacio
authors.initials: H
authors.lastname: Gomez-Acevedo
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blackburn
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Cleves
authors.affiliation: Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
authors.forename: Rohit
authors.initials: R
authors.lastname: Singhal
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D004032:Diet; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007529:Isoflavones / Q000097:blood; D019394:Ki-67 Antigen / Q000235:genetics; D010052:Ovariectomy; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D030262:Soybean Proteins / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D007529:Isoflavones; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D030262:Soybean Proteins; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene
keywords: Endometrial cancer; Estradiol; Selective estrogen receptor modulator; Soy; Uterus