Objectives were to examine mechanisms underlying anabolic actions of
cimaterol in skeletal muscle and to evaluate
cimaterol's actions in hypothyroid and
hyperthyroid rats. In the first study growing rats were fed either a control diet or a diet containing
cimaterol for 10 days. In a second study
sham-thyroidectomized and thyroidectomized (Tx) rats were assigned to one of 5 treatments: control (
sham-Tx), Tx, Tx supplemented with
cimaterol, Tx injected with
triiodothyronine (T3), and Tx rats injected with T3 and supplemented with
cimaterol. Effects of treatments on growth, muscle weights and urinary NT-
methylhistidine (NMH) excretion were evaluated in both trials. Muscle was also collected for determinations of
DNA,
RNA,
protein and activities of several
proteolytic enzymes.
Cimaterol caused muscle
hypertrophy and increased urinary NMH excretion. Hence, anabolic actions of
cimaterol may result from an increase in myofibrillar
protein synthesis which exceeds changes in myofibrillar protein degradation. Urinary NMH excretion was reduced by
thyroidectomy and increased in
hyperthyroid rats and both
hypothyroidism and
hyperthyroidism were characterized by
myopathy.
Cimaterol increased muscle weights in hypothyroid but not in
hyperthyroid rats. Therefore,
cimaterol's anabolic properties are
thyroid hormone-independent and antagonized by excess
thyroid hormone. Anabolic actions of
cimaterol in hypothyroid rat muscle were attributed to an action on
protein synthesis because urinary NMH excretion was not affected by
cimaterol but muscle
RNA concentration was increased. Activities of
cathepsins B, D and L and neutral
proteinase were dose-related to thyroid status, however, were unrelated to
cimaterol-dependent perturbations in NMH excretion. Control of
muscle protein balance by
thyroid hormones may involve regulation of these
enzymes; however, control of
muscle protein degradation by
cimaterol is likely directed towards other proteolytic mechanisms or to mechanisms which alter susceptibility of myofibrillar
proteins to degradation.