Retinoid effects on the epidermis.
Since metaplasia and gap junction stimulation are prominent features of retinoid activity in embryonic and neoplastic epidermis, it is ironic that the mechanism(s) of retinoid action in postnatal tissues, where these drugs are employed clinically, appears to be different. Histologic studies in both animals and man with both topical and systemic retinoids demonstrate acanthosis, hypergranulosis, and changes in the thickness and organization of the stratum corneum, due to a boost in cell turnover. On an ultrastructural level, desmosomes are actively shed at the level of the spinous layer, leading to many new attachment points along the cell membranes of the outer epidermis. This change coupled with decreased tonofilaments, enhanced keratinocyte autolysis, and intercellular deposition of glycoconjugates (not mucin by standard histochemistry and lectin binding) lead to loosening and fragility of the stratum corneum. The biochemical basis of retinoid activity (in addition to increased cell turnover) appears to be global enhancement of glycoconjugate synthesis and the generation of less mature keratins. These epidermal effects of retinoids can be exploited therapeutically: (1) to cause loosening of thickened stratum corneum, e.g., in psoriasis or ichthyosis; (2) to enhance penetration of pharmacologic agents, e.g., 5-FU, across hypertrophic actinic keratoses; and finally (3) in neoplastic epidermis, where mucous metaplasia and gap junction proliferation occur, retinoids can normalize differentiation.
Elias
P M
PM
Dermatology Service, Veterans Administration Medical Center, San Francisco, Calif.
D000818:Animals; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D006001:Glycoconjugates / Q000096:biosynthesis; D006801:Humans; D008679:Metaplasia / Q000139:chemically induced; D012176:Retinoids / Q000009:adverse effects* / Q000627:therapeutic use; D012867:Skin / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced*; D012878:Skin Neoplasms / Q000188:drug therapy
D006001:Glycoconjugates; D012176:Retinoids