Alterations in biochemical composition and ribonucleic acid metabolism induced in rat liver by cortisone.

An investigation of the effect of cortisone administration upon the chemical composition of intracellular particulates of rat liver has been made. Livers were homogenized in 0.25 M sucrose solutions and submitted to differential centrifugation. Five fractions were prepared: mitochondria (Mit), microsomes (Mi), ultracentrifugable (U), non-sedimentable (S), and nuclear (Nuc). Measurement was made of total and polymerized RNA, nitrogen, lipide P, and uptake of P(32) by the RNA of each fraction. The following observations were made:- Cortisone administration caused a fall in concentration in all measured constituents except glycogen. On a per liver basis, however, total liver RNA was unchanged in amount; nitrogen content of Mi fell and that of S increased; the lipide P of Mit and Mi also decreased. The biochemical composition of a statistical mitochondrion was significantly altered; in contrast, the microsomal fraction decreased in amount, but the relationship between the chemical constituents was unchanged. When polymerized RNA was sought by a process involving precipitation from ethanol at 20 degrees C., none was found in the Mit of cortisone livers and the amount in Mi was much less than found in the normal. When, however, precipitation was conducted at 4 degrees C., yields of polymerized RNA in all fractions after cortisone were equal to or greater than those found in the normal. Furthermore, incubation of mixtures of homogenates from normal and cortisone livers resulted in loss of warm precipitable RNA. These data strongly suggest the presence of an enzyme in cortisone livers which upon incubation with normal livers made preparation of polymerized RNA virtually impossible by use of the warm method. This agent, thought to operate in vivo and in vitro, was not present in significant amounts in normal livers, since incubation in this instance had no effect upon the amount of polymerized RNA. Mit from cortisone livers obtained by the cold technique had a significantly decreased rate of incorporation of P(32) even though the yield of RNA from this fraction was increased. To reconcile these observations, it was proposed that under the influence of cortisone a variant of normal RNA is synthesized or normal RNA is converted to this variant. This "new" RNA has new solubility properties, a new rate of incorporation of P(32), and conceivably it cannot act as a template for normal protein synthesis.