Effect of Nutritive State and Precursor Dose on the Incorporation of Orotic Acid and Uridine into Kidney and Liver of Normal, Castrated, and Androgen-treated Mice1

Abstract

The labeling of acid soluble pyrimidines and RNA by radioactive orotic acid and uridine was measured in the kidney and liver of normal, castrated, and androgen-treated mice. The incorporation of [6-14C]-orotic acid injected in doses of 0.5 to 0.6 n-mole into 17-hour fasted mice was approximately twice as high in castrated than in normal andtestosterone propionate-treated castrated mice. In fed animals or in animals fasted only after the injection very little or no difference in labeling was observed. The incorporation of [5-3H]-orotic acid injected in doses of 0.2 to 1.2 nmoles was approximately twice as high in the kidneys of castrated than normal mice, even when the animals were not fasted before the injection. Treatment with testosterone propionate again restored the incorporation to the normal values. Preinjection fasting increased the absolute amounts of radioactivity incorporated by both groups of mice. The difference in labeling between castrated and normal fed mice greatly diminished or entirely disappeared when the dose of orotate injected was increased to 6.0 ixmoles. The incorporation of labeled orotic acid in the liver was not affected by castration, androgen treatment, or nutritional status, and relatively little by increasing the dose of orotic acid. The incorporation of [2-14C]-uridine into the kidney and liver did not show a relationship to hormonal and nutritional status of the mice. The concentration of the acid soluble pyrimidine derivatives was not changed by castration and was slightly affected by starvation. The patterns of radioactivity decay in the acid soluble fraction and the RNA were similar in all three experimental groups following the injection of the labeled precursors. The preferential uptake of the tracer doses of orotic acid in the kidney and its enhancement by fasting is probably related to the fluxes of endogenous substrates in the de novo biosynthetic pathway of UMP. It seems to be the determining factor of the differences in labeling between castrated and normal or testosterone propionatetreated mice. (Endocrinology90: 531, 1972)