TY - JOUR
T1 - Spermidine is not an independent factor regulating limb muscle mass in mice following androgen deprivation
AU - Gordon, Bradley S.
AU - Rossetti, Michael L.
AU - Casero, Robert A.
N1 - Funding Information:
This project was supported by a grant from the Institute of Successful Longevity (B.S.G.) and NIH/NCI RO1CA204345 and University of Pennsylvania Orphan Disease Center Million Dollar Bike Ride no. MDBR-20-135-SRS (R.A.C.).
Publisher Copyright:
© 2021, Canadian Science Publishing. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Maintaining a critical amount of skeletal muscle mass is linked to reduced morbidity and mortality. In males, testicular androgens regulate muscle mass with a loss of androgens being critical as it is associated with muscle atrophy. Atrophy of the limbmuscles is particularly important, but the pathways by which androgens regulate limbmusclemass remain equivocal. We used microarray analysis to identify changes to genes involved with polyamine metabolism in the tibialis anterior (TA) muscle of castrated mice. Of the polyamines, the concentration of spermidine (SPD) was significantly reduced in the TA of castrated mice. To assess whether SPD was an independent factor by which androgens regulate limb muscle mass, we treated castrated mice with SPD for 8 weeks and compared them with sham operated mice. Though this treatment paradigm effectively restored SPD concentrations in the TA muscles of castrated mice, mass of the limb muscles (i.e., TA, gastrocnemius, plantaris, and soleus) were not increased to the levels observed in sham animals. Consistent with those findings, muscle force production was also not increased by SPD treatment. Overall, these data demonstrate for the first time that SPD is not an independent factor by which androgens regulate limb skeletal muscle mass.
AB - Maintaining a critical amount of skeletal muscle mass is linked to reduced morbidity and mortality. In males, testicular androgens regulate muscle mass with a loss of androgens being critical as it is associated with muscle atrophy. Atrophy of the limbmuscles is particularly important, but the pathways by which androgens regulate limbmusclemass remain equivocal. We used microarray analysis to identify changes to genes involved with polyamine metabolism in the tibialis anterior (TA) muscle of castrated mice. Of the polyamines, the concentration of spermidine (SPD) was significantly reduced in the TA of castrated mice. To assess whether SPD was an independent factor by which androgens regulate limb muscle mass, we treated castrated mice with SPD for 8 weeks and compared them with sham operated mice. Though this treatment paradigm effectively restored SPD concentrations in the TA muscles of castrated mice, mass of the limb muscles (i.e., TA, gastrocnemius, plantaris, and soleus) were not increased to the levels observed in sham animals. Consistent with those findings, muscle force production was also not increased by SPD treatment. Overall, these data demonstrate for the first time that SPD is not an independent factor by which androgens regulate limb skeletal muscle mass.
KW - Muscle atrophy
KW - Polyamines
KW - Spermine
KW - Testosterone
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U2 - 10.1139/apnm-2020-0404
DO - 10.1139/apnm-2020-0404
M3 - Article
C2 - 33125852
AN - SCOPUS:85106019688
SN - 1715-5312
VL - 46
SP - 452
EP - 460
JO - Applied Physiology, Nutrition and Metabolism
JF - Applied Physiology, Nutrition and Metabolism
IS - 5
ER -