Estrogen weakens muscle endurance via estrogen receptor-MAPK mediated orosomucoid suppression / 中国药理学与毒理学杂志

ABSTRACT

Gender differences in fatigue, manifesting as female more prone to feel exhausted with lower muscle endurance, still remains unclear mechanism. Here, we investigated whether orosomucoid, an endogenous anti-fatigue protein which can enhance muscle endurance, is involved in this regulation. Female rats showed lower muscle endurance, and this gender difference was disappeared in orosomucoid 1-deficient mice. Female rats also displayed weaker orosomucoid induction in serum, liver and muscle in response to fatigue when compared to male ones. Ovariectomy in female rats results in elevated orosomucoid level and increased swimming time which was reversed by estrogen replenishment, while exogenous estrogen treatment both in male or female mice produced opposite effects. In vitro C2C12 muscle and Chang liver cells, estrogen decreased orosomucoid expression and its promoter activity, and this effect was abolished when estrogen receptor or MAPK was blocked. Thus, estrogen negatively regulates orosomucoid expression, which is responsible for the weaker muscle endurance in females.