Induction of ornithine decarboxylase activity and DNA synthesis in hairless mouse epidermis by retinoids.

The ability of all-trans-retinoic acid (RA) and other retinoid derivatives to enhance DNA synthesis and to induce ornithine decarboxylase [L-ornithine carboxylyase; EC 4.1.1.17 (ODC)] activity has been investigated in normal and tape-stripped hairless mouse epidermis. Initial studies showed that the retinoids could inhibit the induction of epidermal ODC activity found 4.5 hr after tape stripping. Ten nmol RA, 13-cis-retinoic acid (13-cis-RA), ethyl-all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6, 8-nonatetraenoate (aromatic retinoid), or ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8, 8,-tetramethyl-2-naphthyl)-1-propenyl]benzoate (arotinoid ethyl ester) applied topically to the skin at 1 hr before tape stripping inhibited the induction of ODC activity. Induction of epidermal ODC activity was inhibited by arotinoid ethyl ester but not by RA, 13-cis-RA, or aromatic retinoid when they were applied to the skin at 24 hr prior to tape stripping. RA applied topically to normal hairless mouse skin induced a dose-dependent increase in epidermal ODC activity, detectable 24 hr or more after treatment. RA induced epidermal ODC activity to levels only 15- to 30-fold less than found after treatment with the potent tumor promoter tetradecanoylphorbol-13-acetate. Epidermal ODC activity was also induced by topical 13-cis-RA, aromatic retinoid, and arotinoid ethyl ester at this time, although in lower amounts than after RA treatment. The induction of ODC activity by RA was itself inhibited by topical arotinoid ethyl ester treatment. RA, 13-cis-RA, and aromatic retinoid induced ODC activity at doses below those required to enhance epidermal DNA synthesis. In summary, we have shown that, in common with other proliferative stimuli, retinoids can induce ODC activity in hairless mouse epidermis per se. Our results suggest that, because of their ability to also inhibit the expression of ODC activity, the induced ODC activity is found only after the retinoids have been depleted. The ability both to inhibit and to induce ODC activity may be related to the action of RA as a weak tumor promoter under certain conditions and as an inhibitor of promotion under others.