Concomitant modulation of transcripts related to fiber type determination and energy metabolism in skeletal muscle of female ovariectomized mice by estradiol injection

Abstract

In postmenopausal women, prevalence of metabolic syndrome (MS) is 40%. Aging is associated with a decline in basal metabolic rate and an alteration in tissue metabolism, leading to MS. Hormonal therapy has been shown to be effective against some of the MS-related features but its effects on sarcopenia and skeletal muscle metabolism remain unclear. We have analyzed the effects of estradiol (E(2)) on global gene expression in skeletal muscle of ovariectomized (OVX) female C57BL6 mice using the serial analysis of gene expression method. Animals were randomly assigned to six groups of each 14 mice: the vehicle group (OVX), and five groups in which E(2) was injected 1h, 3h, 6h, 18 h or 24h prior to sacrifice. E(2) modulated 177 transcripts, including 11 partially characterized transcripts and 52 potentially novel transcripts. Most of the differentially expressed transcripts were up-regulated at E(2)3h and E(2)18 h, while down-regulated transcripts were observed at E(2)6h and E(2)24h, illustrating two cycles of up and down E(2)-responsive genes. Modulated transcripts were involved in skeletal muscle structure/growth, fiber type distribution and energy metabolism. These results suggest that a single physiological dose of E(2) can concomitantly modulate transcripts determining skeletal muscle type and energy metabolism, which may in turn affect sarcopenia and MS.