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Effect of androgen deprivation therapy on the contractile properties of type I and type II skeletal muscle fibres in men with non‐metastatic prostate cancer
Author(s) -
Lamboley Cedric R,
Xu Hongyang,
Dutka Travis L,
Hanson Erik D,
Hayes Alan,
Violet John A,
Murphy Robyn M,
Lamb Graham D
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12873
Subject(s) - prostate cancer , myosin , endocrinology , medicine , skeletal muscle , androgen deprivation therapy , dithiothreitol , chemistry , androgen , testosterone (patch) , prostate , cancer , hormone , biochemistry , enzyme
Summary The contractile properties of vastus lateralis muscle fibres were examined in prostate cancer (PrCa) patients undergoing androgen deprivation therapy ( ADT ) and in age‐ and activity‐matched healthy male subjects (Control). Mechanically‐skinned muscle fibres were exposed to a sequence of heavily Ca 2+ ‐buffered solutions at progressively higher free [Ca 2+ ] to determine their force‐Ca 2+ relationship. Ca 2+ ‐sensitivity was decreased in both type I and type II muscle fibres of ADT subjects relative to Controls (by −0.05 and −0.04 pC a units, respectively, P < .02), and specific force was around 13% lower in type I fibres of ADT subjects than in Controls ( P = .02), whereas there was no significant difference in type II fibres. Treatment with the reducing agent dithiothreitol slightly increased specific force in type I and type II fibres of ADT subjects (by ~2%‐3%, P < .05) but not in Controls. Pure type II x fibres were found frequently in muscle from ADT subjects but not in Controls, and the overall percentage of myosin heavy chain II x in muscle samples was 2.5 times higher in ADT subjects ( P < .01). The findings suggest that testosterone suppression can negatively impact the contractile properties by (i) reducing Ca 2+ ‐sensitivity in both type I and type II fibres and (ii) reducing maximum specific force in type I fibres.