Estradiol stimulates mitochondrial biogenesis and adiponectin expression in skeletal muscle

Abstract

Sexual dimorphism has been found in mitochondrial features of skeletal muscle, with female rats showing greater mitochondrialmass and function compared withmales. Adiponectin is an insulin-sensitizing adipokinewhose expression has been related tomitochondrial function and that is also expressed in skeletal muscle, where it exerts local metabolic effects. The aim of this research was to elucidate the role of sex hormones inmodulation ofmitochondrial function, as well as its relationshipwith adiponectin production in rat skeletalmuscle. An in vivo studywith ovariectomized Wistar rats receiving or not receiving 17β-estradiol (E2) (10 μg/kg per 48 h for 4 weeks) was carried out, in parallel with an assay of cultured myotubes (L6E9) treated with E2 (10 nM), progesterone (Pg; 1 μM), or testosterone (1 mM). E2 upregulated the markers of mitochondrial biogenesis and dynamics, and also of mitochondrial function in skeletal muscle and L6E9. Although in vivo E2 supplementation only partially restored the decreased adiponectin expression levels induced by ovariectomy, these were enhanced by E2 and Pg treatment in cultured myotubes, whereas testosterone showed no effects. Adiponectin receptor 1 expressionwas increased by E2 treatment, both in vivo and in vitro, but testosterone decreased it. In conclusion, our results are in agreementwith the sexual dimorphismpreviously reported in skeletal muscle mitochondrial function and indicate E2 to be its main effector, as it enhances mitochondrial function and diminishes oxidative stress. Moreover, our data support the idea of the existence of a link betweenmitochondrial function and adiponectin expression in skeletal muscle, which could be modulated by sex hormones. © 2014 Society for Endocrinology.