title: Dietary Genistein Prevents Denervation-Induced Muscle Atrophy in Male Rodents via Effects on Estrogen Receptor-α.
abstract: Genistein has high estrogenic activity. Previous studies have shown beneficial effects of estrogen or hormone replacement therapy on muscle mass and muscle atrophy.
  
  
  
  We investigated the preventive effects and underlying mechanisms of genistein on muscle atrophy.
  
  
  
  In Expt. 1, male Wistar rats were fed a diet containing no genistein [control (CON)] or 0.05% genistein (GEN; wt:wt diet) for 24 d. On day 14, the sciatic nerve in the left hind leg was severed, and the right hind leg was sham-treated. In Expt. 2, male C57BL6J mice were subcutaneously administered a vehicle (Veh group) or the estrogen receptor (ER) antagonist ICI 182,780 (ICI group) via an osmotic pump for 27 d, and each group was subsequently fed CON or GEN diets from day 3 to day 27. Muscle atrophy was induced on day 17 as in Expt. 1. In Expt. 3, male C57BL6J mice were subcutaneously administered vehicle or a selective ER agonist-ER-α [4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT)] or ER-β [2,3-bis(4-hydroxyphenyl)-propionitrile (DPN)]-or genistein (GEN-sc-i) via an osmotic pump for 13 d, and muscle atrophy was induced on day 3 as in Expt. 1. The ratio of denervated soleus muscle weight to sham-operated soleus muscle weight (d/s ratio) was used as the index of muscle atrophy.
  
  
  
  Expt. 1: The d/s ratio in the GEN group was 20% higher than that in the CON group (P < 0.05). Expt. 2: The d/s ratio in the Veh-GEN group was 14% higher than that in the Veh-CON group (P < 0.05), although there was no significant difference between ICI-CON and ICI-GEN groups (P = 0.69). Expt. 3: The d/s ratio in the PPT-treated group was 20% greater than that in the Veh group (P < 0.05), but DPN and GEN-sc-i had no effect on the d/s ratio (P ≥ 0.05 compared with vehicle).
  
  
  
  Genistein intake mitigated denervation-induced soleus muscle atrophy. ER-α was related to the preventive effect of genistein on muscle atrophy.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, and.
authors.forename: Shinya
authors.identifier: 0000-0001-7589-676X
authors.initials: S
authors.lastname: Aoyama
authors.affiliation: "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo, Tokyo, Japan.
authors.forename: Huijuan
authors.identifier: 0000-0001-7909-4940
authors.initials: H
authors.lastname: Jia
authors.affiliation: "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakazawa
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, and.
authors.forename: Junki
authors.initials: J
authors.lastname: Yamamura
authors.affiliation: "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, and "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo, Tokyo, Japan akatoq@mail.ecc.u-tokyo.ac.jp.
authors.forename: Hisanori
authors.identifier: 0000-0001-9140-7698
authors.initials: H
authors.lastname: Kato
mesh_terms: D000818:Animals; D004032:Diet; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors*; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009121:Muscle Denervation / Q000009:adverse effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000188:drug therapy*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011422:Propionates
chemical_list: D004958:Estradiol; D065171:Estrogen Receptor Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D000071161:Forkhead Box Protein O1; D000077267:Fulvestrant; D019833:Genistein; D009419:Nerve Tissue Proteins; D009570:Nitriles; D010636:Phenols; D011720:Pyrazoles; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C467200:Foxo1 protein, mouse; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; C074639:Foxo1 protein, rat
keywords: Foxo1; denervation; estrogen receptor; genistein; skeletal muscle atrophy; ubiquitin ligase