The formation of all-trans-retinoic acid from all-trans-retinol in hairless mouse skin.
All-trans-retinoic acid formation from topically applied retinol has been demonstrated in the skin of skh/hr1 (hairless) mice. The all-trans-retinoic acid was identified on the basis of its chromatographic properties on HPLC at various pH values, its photoisomerization to reaction products identical to those formed from authentic all-trans-retinoic acid, and its co-chromatography with methyl retinoate after methylation with diazomethane. Topically applied retinol is about 2-fold less potent at inducing epidermal hyperplasia and 7-fold less potent at inhibiting the induction of epidermal ornithine decarboxylase by phorbol esters than all-trans-retinoic acid in this strain of mice. To elucidate the possible role all-trans-retinoic acid formation from retinol may have in these pharmacological activities, the epidermal and dermal all-trans-retinoic acid levels were compared in mice treated topically with retinol or [11-3H]-all-trans-retinoic acid. The levels of all-trans-retinoic acid found after retinol treatment were several orders of magnitude lower than those found after [11-3H]-all-trans-retinoic acid treatment, and they were insufficient to account for the difference in potencies between all-trans-retinoic acid and retinol. Retinol was eliminated from the epidermis at a rate similar to that of all-trans-retinoic acid after topical administration, but the initial tissue levels achieved were lower. These results suggest that the lower potencies of retinol may simply reflect lower tissue uptake.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004790:Enzyme Induction / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D005260:Female; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D006965:Hyperplasia; D051379:Mice; D008812:Mice, Hairless; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism*; D013053:Spectrophotometry; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D014801:Vitamin A / Q000378:metabolism* / Q000494:pharmacology
D014801:Vitamin A; D014212:Tretinoin; D009955:Ornithine Decarboxylase