Messenger RNA for enzymes of ornithine and polyamine metabolism are selectively underexpressed in kidney of 5/6 nephrectomized rats.

Altered nitrogen metabolism is a feature of chronic renal failure (CRF). The present study examined changes in renal expression of mRNA for enzymes involved in ornithine and polyamine metabolism, i.e. ornithine aminotransferase (OAT), ornithine decarboxylase (ODC), and S-adenosylmethionine synthetase (S-ADMase), during the early phase of renal insufficiency in rats after 5/6 nephrectomy (Nx). Involvement of androgens, the most potent stimulators of renal ODC, in these changes, was also evaluated inasmuch as testoseronemia is known to be significantly decreased in male uremic subjects. The abundance of mRNA was evaluated by quantitative Northern analysis of total RNA extracted from the remnant kidney of male or female Nx rats. The level mRNA for ODC was depressed by 76, 83, and 79%, that for OAT by 60, 76 and 63%, and that for S-ADMase by 37, 58 and 30%, at, respectively, 2, 7 and 35 days after Nx, in both male and female rats. ODC but not OAT enzyme activity was decreased. The expression of glyceraldehyde-3-phosphate dehydrogenase was only slightly lowered and that of c-myc was unaltered. Renal polyamine content of the remnant kidney was unchanged. It is concluded that in CRF: (1) intrarenal ornithine metabolism and polyamine biosynthesis are greatly impaired; (2) decreased androgens are not involved in these changes; (3) increased ODC is not a prerequisite for kidney hypertrophy; (4) extrarenal polyamines accumulation into the remnant likely compensates for defective renal biosynthesis.