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


METHODS
Human skeletal muscle cells were treated with 10 nm oestradiol, 5 microm TAM and 10 microm RAL over a 24-h period. Following the treatment period, mRNA expression was quantified using real-time PCR to detect changes in ER-alpha, ER-beta, steroid receptor coactivator (SRC), silencing mediator for retinoid and thyroid hormone receptors (SMRT), MyoD, GLUT4 and c-fos.


RESULTS
ER-alpha mRNA expression increased with all three drug treatments (P < 0.05) while there was no change in mRNA expression of ER-beta 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).


CONCLUSIONS
These findings are novel in that they provide the first evidence that oestradiol and selective ER modulators influence ER-alpha 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.
Division of Biokinesiology and Physical Therapy, Clinical Exercise Research Center, Los Angeles, CA, USA.
C M
CM
Dieli-Conwright
T M
TM
Spektor
J C
JC
Rice
E
E
Todd Schroeder
D004958:Estradiol / Q000494:pharmacology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D056985:Nuclear Receptor Co-Repressor 2 / Q000096:biosynthesis / Q000187:drug effects*; D056920:Nuclear Receptor Coactivator 1 / Q000096:biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology
D056985:Nuclear Receptor Co-Repressor 2; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D056920:Nuclear Receptor Coactivator 1