TOPICAL RETINALDEHYDE INCREASES SKIN CONTENT OF RETINOIC ACID AND EXERTS BIOLOGIC ACTIVITY IN MOUSE SKIN

Retinaldehyde, a natural metabolite of beta-carotene and retinol, has been proposed recently for topical use in humans, Because retinaldehyd e does not bind to retinoid nuclear receptors, its biologic activity s hould result from enzymatic transformation by epidermal keratinocytes into ligands for these receptors, such as all-trans retinoic acid and 9-cis-retinoic acid, In this study, we analyzed by high performance li quid chromatography the type and amounts of tissue retinoids as well a s several biologic activities resulting from topical application of ei ther retinaldehyde or all-trans retinoic acid on mouse tail skin, Biol ogic activities of ah-trans retinoic acid and retinaldehyde were quali tatively identical in metaplastic parameters (induction of orthokerato sis, reduction of keratin 65-kDa mRNA, increase in filaggrin and loric rin mRNAs) and hyperplastic parameters (increase in epidermal thicknes s, increase in bromodeoxyuridine (BrdU)-positive cells, increase in ke ratin 50-kDa mRNA, and reduction in keratin 70-kDa mRNA), Some quantit ative differences, not all in favor of all-trans retinoic acid, were f ound in several indices, Cellular retinoic acid-binding protein II and cellular retinol-binding protein I mRNAs were increased by both topic al retinaldehyde and all-trans retinoic acid, Whereas all-trans retino ic acid, 9-cis-retinoic acid, and 13-cis-retinoic acid were not detect able (limit 5 ng/g) in vehicle-treated skin, 0.05% retinaldehyde-treat ed skin contained 13 +/- 6.9 ng/g wet tissue of all-trans retinoic aci d (mean +/- SD), 12.6 +/- 5.9 ng/g 13-cis-retinoic acid, and no 9-cis- retinoic acid, In contrast, 9-cis-retinoic acid was detectable in 0.05 % of ah-trans retinoic acid-treated skin, which also contained 25-fold more all-trans retinoic acid and 5-fold more 13-cis-retinoic acid tha n retinaldehyde-treated skin, Our results show that topical retinaldeh yde is transformed in vivo into all-trans retinoic acid by mouse epide rmis, The small amounts of ligand for retinoic acid nuclear receptors thus produced are sufficient to induce biologic effects similar to tho se resulting from the topical application of the ligand itself in much higher concentration.