Previous study suggests that estrogen could be opposed to the development of cardiac hypertrophy. However, the mechanisms of E2 action are obscure. Additionally, activation of serine/threonine protein phosphatase1 (PP1) involvesthe cardiac hypertrophy induced by b-adrenergic signaling. In this study, we treated H9c2 cardiomyocytes with isoproterenol (ISO) which stimulates β-adrenergic receptor and contributes to cardiomyocyte hypertrophy, which shares similarity to end-stage human heart failure. The results show that the extent of cardiomyocyte hypertrophy increase in respond to ISO stimulation. Pretreatment of 17β-estradiol (E2), tet-on estrogen receptor-α, or both of them significantly prevented ISO- induced increased cell size. Additionally, estrogen receptor antagonist (ICI) could reverse those effects, suggesting E2 action is partially through estrogen receptor. Furthermore, Pretreatment of 17β-estradiol (E2), tet-on estrogen receptor-α, or both reduce ISO-induced protein phosphatase1 (PP1) protein expression, activity, and increase the level of Ser-16 phosphorylated phospholamban(PLB), a downstream protein of protein phosphatase 1 and responsible for regulation of sarcoplasmic reticulum Ca2＋-ATPase (SERCA) activity. Taken together, we suggest that estrogen inhibit cardiomyocyte hypertrophy, possibly through interfering protein phosphatase1 (PP1) function and its downstream signaling.
