Effect of the antiglucocorticoid RU38486 on protein metabolism in unweighted soleus muscle

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Abstract

Unweighting the hindlimbs by tail suspension of juvenile rats leads to atrophy of the soleus muscle, especially during the third day of unweighting. Although a previous study using adrenalectomized animals suggested a minimal role of glucocorticoids in this atrophy, the inability of adrenalectomized animals to release other adrenal hormones could have been important. Therefore, the influence of oral administration of RU38486 [11-β-(4-dimethylaminophenyl) 17-β-hydroxy 17-α(prop-1-ynyl) estra 4,9-dien 3-one], a selective glucocorticoid antagonist, on protein metabolism in the unweighted soleus was studied. The effectiveness of RU38486 treatment was demonstrated in hindlimb-suspended rats as the drug abolished the increase in soleus glutamine synthetase activity shown previously to be caused by elevated circulating glucocorticoids. The slower weight gain of suspended rats was unaffected by the drug. After 3 days of unweighting, the difference in protein content from weighted soleus muscle was not diminished significantly by RU38486 (-25%, vehicle only; -18%, RU38486-treated). However, in both weight-bearing and suspended animals, RU38486 seemed to promote protein accretion between days 2 and 3 of the experiment; ie, unweighted muscle seemed to lose less protein. All suspended animals showed slower (-58% to -64%) fractional in vivo rates of synthesis. RU38486 did not affect these percent differences in fractional protein synthesis after either 2 or 3 days of unweighting. The apparent improvement in protein balance likely resulted from a decline in protein degradation in both the weight-bearing (-26%) and unweighted (-35%) soleus. Since this glucocorticoid antagonist had similar effects in soleus muscle of both weight-bearing and suspended rats, it is unlikely that unweighting atrophy is a consequence of elevated circulating glucocorticoids or increased muscle binding capacity for these hormones.

Original languageEnglish (US)
Pages (from-to)1451-1455
Number of pages5
JournalMetabolism
Volume43
Issue number11
DOIs
StatePublished - Nov 1994

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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