β-MyHC exerts a dominant effect in heart failure and is a mechanism behind impairments in contractile function. (A) β-MyHC (expressed as a percentage of total MyHC content) is increased in hearts from 8-month-old mice consuming a soy diet. n = 3–7 in each group. *P < 0.05 versus WT same sex and diet and same sex, alternate diet HCM mice. ^†P < 0.05 versus alternate sex, same diet HCM mice. (B) Representative silver-stained MyHC separation gel from WT male and HCM male mice. (C) Increased activation of the IGF-1 receptor upregulates MyHC protein in the heart. GSK3β is a protein kinase downstream from the IGF receptor. The ratio of phospho- to total GSK3β is significantly attenuated in the males consuming a phytoestrogen-free diet. The increased activity down this cascade may be permissive of increased β-MyHC protein synthesis. n = 5 in each group. **P < 0.05 versus WT same sex and diet; ^#P < 0.05 versus alternate diet, same sex HCM mice and alternate sex HCM mice regardless of diet. Mean ± SEM.