Oestradiol and SERM treatments influence oestrogen receptor coregulator gene expression in human skeletal muscle cells

• Published in: Acta Physiologica 2009-11, Vol.197 (3), p.187-196
• Main Authors: Dieli-Conwright, C.M, Spektor, T.M, Rice, J.C, Todd Schroeder, E
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Estradiol - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Regulation - drug effects; Humans; Muscle Cells - drug effects; Muscle Cells - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; MyoD; Nuclear Receptor Co-Repressor 2 - biosynthesis; Nuclear Receptor Co-Repressor 2 - drug effects; Nuclear Receptor Coactivator 1 - biosynthesis; Nuclear Receptor Coactivator 1 - drug effects; Raloxifene Hydrochloride - pharmacology; Receptors, Estrogen - drug effects; Receptors, Estrogen - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Selective Estrogen Receptor Modulators - pharmacology; skeletal muscle; SMRT; SRC; Tamoxifen - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2009.01997.x

Oestrogen receptors (ER) are present in human skeletal muscle (hSkM) cells; however, the function of the receptor is currently unknown. We investigated the influence of oestradiol and selective ER modulators [tamoxifen (TAM), raloxifene (RAL)] on ER coregulator mRNA expression in hSkM. Human skeletal muscle cells were treated with 10 n m oestradiol, 5 μ m TAM and 10 μ m RAL over a 24-h period. Following the treatment period, mRNA expression was quantified using real-time PCR to detect changes in ER-α, ER-β, steroid receptor coactivator (SRC), silencing mediator for retinoid and thyroid hormone receptors (SMRT), MyoD, GLUT4 and c-fos. ER-α mRNA expression increased with all three drug treatments (P < 0.05) while there was no change in mRNA expression of ER-β in hSkM cells. mRNA expression of SRC increased and SMRT decreased with oestradiol, TAM and RAL in hSkM cells (P < 0.05). Importantly, mRNA expression of MyoD increased with oestradiol and decreased with TAM and RAL in hSkM cells (P < 0.05). mRNA expression of GLUT4 increased with oestradiol and RAL and decreased with TAM in hSkM cells (P < 0.05). These findings are novel in that they provide the first evidence that oestradiol and selective ER modulators influence ER-α function in hSkM cells. This demonstrates the importance of the ER and alterations in its coregulators, to potentially prevent sarcopenia and promote muscle growth in postmenopausal women using these forms of hormone replacement therapy.