title: Differential effects of short term feeding of a soy protein isolate diet and estrogen treatment on bone in the pre-pubertal rat.
abstract: BACKGROUND
  Previous reports suggest that beneficial effects of soy on bone quality are due to the estrogenic actions of isoflavone phytochemicals associated with the protein. However, mechanistic studies comparing the effects of soy diet and estrogens on bone, particularly in rapidly growing animals are lacking.
  
  
  RESULTS
  We studied the effects of short term feeding of soy protein isolate (SPI) on bone in comparison to the effects of 17β-estradiol (E2) in pre-pubertal rats. Female rats were weaned to one of 4 treatments: 1) a control casein-based diet (CAS); 2) CAS with subcutaneous E2 (10 µg/kg/d) (CAS+E2); 3) a SPI-containing diet (SPI); or 4) SPI with subcutaneous E2 (SPI) or SPI with 10 µg/kg/d E2 (SPI+E2) for 14 days beginning on postnatal day 20. SPI increased while E2 decreased bone turnover compared to CAS. In contrast, both treatments decreased serum sclerostin levels. Microarray analysis of RNA isolated from bone revealed 652 genes regulated by SPI, 491 genes regulated by E2, and 266 genes regulated by both SPI diet and E2 compared to CAS. The expression of caveolin-1, a protein localized in the cell membrane, was down-regulated (p<0.05) in rats fed SPI, but not by E2 compared to rats fed casein. Down-regulation of caveolin-1 by SPI was associated with increased BMP2, Smad and Runx2 expression in bone and osteoblasts (p<0.05).
  
  
  CONCLUSIONS
  These results suggest SPI and E2 have different effects on bone turnover prior to puberty. Approximately half of the genes are regulated in the same direction by E2 or SPI, but in combination, SPI blocks the estrogen effects and returns the profile towards control levels. In addition, there are E2 specific and SPI-specific gene changes related to regulation of bone formation.
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, Arkansas, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Oxana P
authors.initials: OP
authors.lastname: Lazarenko
authors.forename: Xianli
authors.initials: X
authors.lastname: Wu
authors.forename: Yudong
authors.initials: Y
authors.lastname: Tong
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blackburn
authors.forename: Horatio
authors.initials: H
authors.lastname: Gomez-Acevedo
authors.forename: Kartik
authors.initials: K
authors.lastname: Shankar
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.forename: Martin J J
authors.initials: MJ
authors.lastname: Ronis
authors.forename: Jin-Ran
authors.initials: JR
authors.lastname: Chen
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D001862:Bone Resorption / Q000097:blood; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002116:Calcitonin / Q000235:genetics / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004044:Dietary Proteins / Q000008:administration & dosage*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers / Q000235:genetics; D007529:Isoflavones / Q000097:blood; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation; D015398:Signal Transduction; D030262:Soybean Proteins / Q000008:administration & dosage*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D051700:Activating Transcription Factor 3; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D051242:Caveolin 1; D050659:Core Binding Factor Alpha 1 Subunit; D004044:Dietary Proteins; D005819:Genetic Markers; D007529:Isoflavones; C493717:Runx2 protein, rat; C486031:Sost protein, rat; D030262:Soybean Proteins; D015675:Osteocalcin; D004958:Estradiol; D002116:Calcitonin; D000469:Alkaline Phosphatase