17β-estradiol upregulates the expression of peroxisome proliferator-activated receptor α and lipid oxidative genes in skeletal muscle

This study examined the actions of 17beta-estradiol (E-2) and progesterone on the regulation of the peroxisome proliferator-activated receptors (PPARalpha and PPARgamma) family of nuclear transcription factors and the mRNA abundance of key enzymes involved in fat oxidation, in skeletal muscle. Specifically, carnitine palmitoyltransferase I (CPT I), beta-3-hydroxyacyl CoA dehydrogenase (beta-HAD), and pyruvate dehydrogenase kinase 4 (PDK4) were examined. Sprague-Dawley rats were ovariectomized and treated with placebo (Ovx), E-2 progesterone, or both hormones in combination (E+P). Additionally, sham-operated rats were treated with placebo (Sham) to serve as controls. Hormone (or vehicle only) delivery was via time release pellets inserted at the time of surgery, 15 days prior to analysis. E-2 treatment increased PPARalpha mRNA expression and protein content (P<0.05), compared with Ovx treatment. E-2 also resulted in upregulated mRNA of CPT I and PDK4 (P<0.05). PPARgamma mRNA expression was also increased (P<0.05) by E-2 treatment, although protein content remained unaltered. These data demonstrate the novel regulation of E-2 on PPARalpha and genes encoding key proteins that are pivotal in regulating skeletal muscle lipid oxidative flux. Journal of Molecular Endocrinology (2003).