Induction of spermidine N1-acetyltransferase by 1 alpha,25-dihydroxyvitamin D3 as an early common event in the target tissues of vitamin D.

We have reported that the duodenal ornithine decarboxylase activity and the tissue content of putrescine increase markedly after a single intravenous injection of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) into vitamin D-deficient chicks (Shinki, T., Takahashi, N., Miyaura, C., Samejima, K., Nishii, Y., and Suda, T. (1981) Biochem. J. 195, 685-690). In the present study, we examined in the same experimental system the effect of 1 alpha,25(OH)2D3 on the activity of duodenal spermidine N1-acetyltransferase, a rate-limiting enzyme catalyzing the conversion from spermidine to putrescine. The duodenal spermidine N1-acetyltransferase activity began to increase 30 min after a single intravenous injection of 625 ng of 1 alpha,25(OH)2D3 and attained a maximum in 2 h. As little as 1.25 ng of 1 alpha,25(OH)2D3 induced a small but significant increase in the spermidine N1-acetyltransferase activity, and the maximal response was obtained by 125 ng of the vitamin. The dose levels of 1 alpha,25(OH)2D3 required to induce duodenal spermidine N1-acetyltransferase activity were only one-tenth as much as those required to induce ornithine decarboxylase activity. The spermidine N1-acetyltransferase activity was induced commonly in the target tissues of vitamin D, whereas ornithine decarboxylase activity occurred only in intestine. The 1 alpha,25(OH)2D3-induced spermidine N1-acetyltransferase activity was greatly inhibited by prior administration of actinomycin D or cycloheximide. When 30,000 X g intestinal supernatants were incubated with [14C]spermidine, [14C]putrescine was formed. These results clearly indicate that the induction of spermidine N1-acetyltransferase activity is the 1 alpha,25(OH)2D3-induced earliest de novo synthesis in several proteins induced by the vitamin reported to date and that the 1 alpha,25(OH)2D3-induced duodenal synthesis of putrescine occurs by the pathways from both ornithine and spermidine.