Tissue Selective Androgen Receptor Modulators (SARMs) Increase Pelvic Floor Muscle Mass in Ovariectomized Mice.
Stress urinary incontinence (SUI), a prevalent condition, is represented by an involuntary leakage of urine that results, at least in part, from weakened or damaged pelvic floor muscles and is triggered by physical stress. Current treatment options are limited with no oral therapies available. The pelvic floor is rich in androgen receptor and molecules with anabolic activity including selective androgen receptor modulators (SARMs) may serve as therapeutic options for individuals with SUI. In this study, two SARMs (GTx-024 and GTx-027) were evaluated in a post-menopausal animal model in order to determine their effect on pelvic floor muscles. Female C57BL/6 mice were ovariectomized and their pelvic muscles allowed to regress. The animals were then treated with vehicle or doses of GTx-024 or GTx-027. Animal total body weight, lean body mass, and pelvic floor muscle weights were measured along with the expression of genes associated with muscle catabolism. Treatment with the SARMs resulted in a restoration of the pelvic muscles to the sham-operated weight. Coordinately, the induction of genes associated with muscle catabolism was inhibited. Although a trend was observed towards an increase in total lean body mass in the SARM-treated groups, no significant differences were detected. Treatment of an ovariectomized mouse model with SARMs resulted in an increase in pelvic floor muscles, which may translate to an improvement of symptoms associated with SUI and serves as the basis for evaluating their clinical use. J. Cell. Biochem. 118: 640-646, 2017. © 2016 Wiley Periodicals, Inc.
Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
Suriyan
S
Ponnusamy
Department of Comparative Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
Ryan D
RD
Sullivan
Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
Thirumagal
T
Thiyagarajan
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Heather
H
Tillmann
GTx Inc, Memphis, Tennessee.
Robert H
RH
Getzenberg
Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.|West Cancer Center, Memphis, Tennessee.
Ramesh
R
Narayanan
D059002:Androgen Receptor Antagonists / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D017773:Pelvic Floor; D011944:Receptors, Androgen / Q000378:metabolism*; D014550:Urinary Incontinence, Stress / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D059002:Androgen Receptor Antagonists; D000813:Anilides; D011944:Receptors, Androgen; C547106:ostarine
ANDROGEN; INCONTINENCE; SARM; SUI