Polyamine metabolism during cardiac hypertrophy

Treatment with thyroxine for 7 days to produce myocardial hypertrophy led to an increase in the content of putrescine, spermidine, and spermine in the rat heart. The content of decarboxylated S-adenosylmethionine, the source of the aminopropyl groups needed for polyamine synthesis, was increased by the thyroxine treatment as were the activities of ornithine and S-adenosylmethionine decarboxylases. The enhanced S-adenosylmethionine decarboxylase activity measured in vitro was due to an increase in the amount of enzyme protein as measured by immunotitration with a specific antiserum. In vivo, decarboxylation of S-adenosylmethionine was, therefore, increased both by the increased amount of enzyme protein and by the elevated concentration of putrescine (which activates the enzyme) brought about by the enhanced ornithine carboxylase activity. Spermine synthase did not change significantly during the treatment and spermidine synthase increased only slightly. Therefore, the accumulation of polyamines was mediated predominantly via the increased availability of both putrescine and decarboxylated S-adenosylmethionine. Administration of 1,3-diamino-2-propanol led to a rapid reduction in the activity of ornithine decarboxylase in the heart, and continued exposure to this substance by its inclusion in the drinking water completely prevented the increase in concentration of putrescine and polyamines in response to thyroxine. However, cardiac hypertrophy as measured by the increase in cardiac mass was not prevented by such treatment with 1,3-diaminopropanol, showing that the increased content of polyamines was not essential for the hypertrophic response.