Studies on the role of polyamines in the proliferation of mouse epidermis (Japanese)

The activity of ornithine decarboxylase in mouse skin increased very rapidly after a single application of ethylphenylpropiolate (EPP), a potent hyperplasiogenic agent of the epidermis. It reached a maximum, after 8 hr and then decreased, in the next 5 hr to one fifth of the maximum. S-Adenosylmethionine decarboxylase was induced by EPP but increase in its activity was slower and less pronounced than that of ornithine decarboxylase. The tissue concentration of putrescine changed in parallel with alteration of ornithine decarboxylase activity and was maximal 8 hr after EPP treatment. The spermidine level decreased significantly 4-6 hr after EPP treatment, when putrescine formation from spermidine was accelerated, and increased to 30% more than the normal level at 28 hr. The spermine level did not change within 28 hr after EPP treatment. The highest activity of DNA synthesis was observed at 24 hr, and the mitotic activity of basal cells reached the maximum 36 hr after the application of EPP. Administration of DL-α-hydrazino-δ-aminovaleric acid (DL-HAVA), a potent and fairly specific inhibitor of ornithine decarboxylase, greatly depressed the increase in putrescine level in EPP-stimulated mouse skin, but had little effect on the change in spermidine concentration. Under the same conditions, examination of DNA synthesis and the histologic appearance of the skin showed that DL-HAVA also inhibited induction of cell proliferation by EPP. The inhibition by DL-HAVA was reversed by administration of putrescine, but not cadaverine or 1,7-diaminoheptane. It is suggested that the rise in the putrescine level induced by EPP is a requisite for subsequent cell proliferation of the epidermis of mice.