title: Transcriptional regulation of myotrophic actions by testosterone and trenbolone on androgen-responsive muscle.
abstract: Androgens regulate body composition and skeletal muscle mass in males, but the molecular mechanisms are not fully understood. Recently, we demonstrated that trenbolone (a potent synthetic testosterone analogue that is not a substrate for 5-alpha reductase or for aromatase) induces myotrophic effects in skeletal muscle without causing prostate enlargement, which is in contrast to the known prostate enlarging effects of testosterone. These previous results suggest that the 5α-reduction of testosterone is not required for myotrophic action. We now report differential gene expression in response to testosterone versus trenbolone in the highly androgen-sensitive levator ani/bulbocavernosus (LABC) muscle complex of the adult rat after 6weeks of orchiectomy (ORX), using real time PCR. The ORX-induced expression of atrogenes (Muscle RING-finger protein-1 [MuRF1] and atrogin-1) was suppressed by both androgens, with trenbolone producing a greater suppression of atrogin-1 mRNA compared to testosterone. Both androgens elevated expression of anabolic genes (insulin-like growth factor-1 and mechano-growth factor) after ORX. ORX-induced increases in expression of glucocorticoid receptor (GR) mRNA were suppressed by trenbolone treatment, but not testosterone. In ORX animals, testosterone promoted WNT1-inducible-signaling pathway protein 2 (WISP-2) gene expression while trenbolone did not. Testosterone and trenbolone equally enhanced muscle regeneration as shown by increases in LABC mass and in protein expression of embryonic myosin by western blotting. In addition, testosterone increased WISP-2 protein levels. Together, these findings identify specific mechanisms by which testosterone and trenbolone may regulate skeletal muscle maintenance and growth.
authors.affiliation: Geriatric Research, Education and Clinical Center, VA Medical Center, Gainesville, FL, United States; Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, United States. Electronic address: evan1979@ufl.edu.
authors.forename: Fan
authors.initials: F
authors.lastname: Ye
authors.affiliation: Rural Health, VA Medical Center, Gainesville, FL, United States; Animal Sciences, University of Florida, Gainesville, FL, United States.
authors.forename: Sean C
authors.initials: SC
authors.lastname: McCoy
authors.affiliation: Physical Therapy, University of Florida, Gainesville, FL, United States.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Ross
authors.affiliation: Physical Therapy, University of Florida, Gainesville, FL, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Bernardo
authors.affiliation: Physical Therapy, University of Florida, Gainesville, FL, United States.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Beharry
authors.affiliation: Physical Therapy, University of Florida, Gainesville, FL, United States.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Senf
authors.affiliation: Physical Therapy, University of Florida, Gainesville, FL, United States.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Judge
authors.affiliation: Geriatric Research, Education and Clinical Center, VA Medical Center, Gainesville, FL, United States.
authors.forename: Darren T
authors.initials: DT
authors.lastname: Beck
authors.affiliation: Geriatric Research, Education and Clinical Center, VA Medical Center, Gainesville, FL, United States.
authors.forename: Christine F
authors.initials: CF
authors.lastname: Conover
authors.affiliation: Geriatric Research, Education and Clinical Center, VA Medical Center, Gainesville, FL, United States.
authors.forename: Darryl F
authors.initials: DF
authors.lastname: Cannady
authors.affiliation: Physical Therapy, University of Florida, Gainesville, FL, United States.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Smith
authors.affiliation: Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, United States; Research, VA Medical Center, Gainesville, FL, United States.
authors.forename: Joshua F
authors.initials: JF
authors.lastname: Yarrow
authors.affiliation: Geriatric Research, Education and Clinical Center, VA Medical Center, Gainesville, FL, United States; Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, United States.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Borst
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D055511:CCN Intercellular Signaling Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D009133:Muscular Atrophy / Q000235:genetics; D009218:Myosins / Q000378:metabolism; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012038:Regeneration / Q000187:drug effects; D012097:Repressor Proteins / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014204:Trenbolone Acetate / Q000494:pharmacology*
chemical_list: D000728:Androgens; D055511:CCN Intercellular Signaling Proteins; C115044:CCN5 protein, rat; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D013739:Testosterone; D009218:Myosins; D014204:Trenbolone Acetate
keywords: Androgen; Atrophy; Hypertrophy; Hypogonadism; Skeletal muscle