Regulation of androgen receptor expression at the onset of functional overload in rat plantaris muscle

Integrative Muscle Biology Laboratory, Exercise Science Department, University of South Carolina, Columbia South Carolina 29208 Submitted 15 April 2003 ; accepted in final form 25 July 2003 Skeletal muscle androgen receptor (AR) expression at the onset of functional overload (OV) has not been well described. It is also not known if overload and/or anabolic steroid differentially regulate AR expression. The purpose of this study was to examine AR gene expression at the onset of functional OV in rat plantaris muscle with and without nandrolone decanoate (ND) administration. The functional significance of AR protein induction was examined using skeletal -actin promoter activity in transiently transfected CV-1 fibroblast cells. Male Sprague-Dawley rats ( 125 g) were functionally overloaded for 1, 3, 7, or 21 days. A subset of animals was given an ND (6 mg/kg) injection at day 0 and then overloaded for 3 days. Control animals underwent sham surgeries. AR protein concentration increased 106 and 279% after 7 and 21 days of OV, respectively. AR mRNA increased 430% after 7 days of OV. AR protein expression in C2C12 murine myotubes subjected to 1% chronic radial stretch for 18 h was elevated 101% compared with control. ND treatment increased AR protein concentration 1,300% compared with controls, and there was no additional effect when ND and OV were combined. ND with 3 days of OV treatment increased AR mRNA expression 50% compared with control. AR overexpression in transiently transfected CV-1 fibroblast cells increased -424 bp skeletal -actin promoter activity 80 to 1,800% in a dose-dependent fashion. Co-overexpression of either serum response factor (SRF) or active RhoA with AR overexpression induced a synergistic 36- and 28-fold induction of skeletal -actin promoter. Cotransfection of AR, SRF, and active RhoA induced 180-fold increase in skeletal -actin promoter activity. In conclusion, AR protein expression is increased after 7 days of functional OV, and this induction is regulated pretranslationally. AR induction in conjunction with SRF and RhoA signaling may be an important regulator of gene expression during overload-induced muscle growth. anabolic steroids; steroid receptors; mechanical signaling Address for reprint requests and other correspondence: J. A. Carson, Univ. of South Carolina, Dept. of Exercise Science, 1300 Wheat St., Columbia SC 29208 (E-mail: carsonj{at}sc.edu ).