Ornithine metabolism along the female mouse nephron: localization of ornithine decarboxylase and ornithine aminotransferase

Abstract

The fate of ornithine in the nephron of the female OF-1 Swiss mouse remains unknown. The aim of the present study was to identify the nephron segments containing the key enzymes involved in ornithine metabolism: ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT). Viable tubules isolated by microdissection were incubated with [1-¹⁴C]ornithine to study the oxidative pathway. Other tubules were permeabilized to measure the ODC activity. Ornithine was decarboxylated in all intact tubules. Gabaculine, a suicide inhibitor of OAT, and rotenone sharply decreased the production of ¹⁴CO₂ from [1-¹⁴C]ornithine. No ODC activity was found in permeabilized tubules isolated from untreated mice. Testosterone increased ODC activity in the proximal tubule substantially and to a minor extent in other nephron segments. In situ hybridization showed ODC messenger ribonucleic acid (mRNA) to be absent in kidneys of untreated females but abundant in the cortex and the outer stripe of the outer medulla of testosterone-treated female mice. The whole proximal tubule contained a great density of silver grains corresponding to ODC mRNA. In conclusion, no basal ODC activity was found in the nephron of female mice. The testosterone-inducible ODC is localized mainly in the proximal tubule, but is also present in distal tubules and collecting ducts. OAT is distributed along the whole nephron, but its activity is higher in proximal tubules than in distal tubules.