Epidermal effects of retinoids: supramolecular observations and clinical implications.
Retinoids, synthetic vitamin A analogs, stimulate mucous metaplasia and gap-junction proliferation in embryonic and neoplastic epidermis. Such effects demonstrate that vitamin A has potent effects on epidermal differentiation. Oddly, however, retinoid action in normal postnatal tissues, where these drugs are used clinically, appears to be quite different. In animals and humans, both topical and systemic retinoids produce acanthosis, hypergranulosis, and a relative (but not absolute) decrease in the thickness of the stratum corneum. These changes reflect the distinct boost in cell turnover that results from retinoid treatment. On the ultrastructural level, desmosomes are actively shed by cells of the spinous layer, resulting in many fewer attachment points along the cell membranes of the outer epidermis. Loss of desmosomes, coupled with decreased tonofilaments, enhanced keratinocyte autolysis, and intercellular deposition of glycoconjugates (not mucin), cause loosening and fragility of the stratum corneum (so-called anti-keratinizing effects). The biochemical basis of retinoid activity, in addition to stimulating increased cell turnover, appears to be a global enhancement of glycoconjugate synthesis and the generation of less mature keratins. The epidermal effects of retinoids can be exploited therapeutically: to cause loosening of thickened stratum corneum, for example in psoriasis or ichthyosis; to enhance penetration of pharmacologic agents such as 5-fluorouracil across hypertrophic actinic keratoses; and to normalize differentiation in neoplastic epidermis involving mucous metaplasia and gap-junction proliferation.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003896:Desmosomes / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects; D007633:Keratins / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology* / Q000633:toxicity; D012871:Skin Diseases / Q000188:drug therapy
D012176:Retinoids; D007633:Keratins