Independence of enhanced protein catabolism from glucocorticoids in chronically uremic rats

Abstract

Patients with chronic renal failure are prone to develop negative nitrogen balance resulting clinically in wasting and malnutrition. To study the role of glucocorticoids in the pathogenesis of uremic catabolism, we determined urinary excretion rates of urea and Nt-methylhistidine in chronically uremic rats with and without RU 38486, a potent antiglucocorticoid. In comparison to pair-fed non-uremic animals, chronically uremic rats displayed significantly enhanced ureagenesis, as demonstrated by increased urinary urea excretion, and myofibrillar protein breakdown, as indicated by increased excretion rates of urinary Nt-methylhistidine. The administration of RU 38486 to chronically uremic rats, however, did not result in a normalization of urinary excretion of Nt-methylhistidine. Similarly, the antiglucocorticoid did not influence the extent of ureagenesis in our uremic animals, as it was demonstrated by comparable levels of urinary urea excretion. This suggests that glucocorticoids are not involved in the pathogenesis of enhanced catabolism in chronic renal insufficiency.

Antiglucocorticoid RU38486 reduces net protein catabolism in experimental acute renal failure

“…While this result is in contrast to Schäfer et al [6,8], Lowell et al . found no reduction of the efflux of 3-methylhistidin after adrenalectomy in the perfused hindquarter of fasted animals [50], and in rats with chronic uremia, RU38486- resistant protein catabolism with unchanged release of 3-methylhistidin has been demonstrated in vivo by Teschner [51]. As responsiveness of protein synthesis and degradation to amino acid availability seem to be regulated differentially [52] and activation of glucocorticoid- mediated proteolysis occurs only at relatively elevated hormone levels [53] compared to the inhibition of protein synthesis [54], it seems possible to speculate that RU38486 may have a more pronounced effect on net protein catabolism at substantially higher doses.…”