Human in vivo pharmacology of topical retinoids.
All-trans retinoic acid is used topically for treating a variety of dermatologic conditions ranging from acne to photoaged skin. Although the clinical effects of retinoic acid treatment are often considerable, relatively little is known about the basic mechanisms underlying such effects. With the development of an in vivo human assay we have investigated the pleiotypic effects of topical retinoids from the histologic to the molecular. Histologically, retinoic acid induces epidermal proliferation and differentiation coupled with dermal fibroblast production of collagen. Immunologic effects include stimulation of the antigen-presenting capacity of Langerhans cells and induction of keratinocyte ICAM-1 expression. At the biochemical level, retinoic acid regulates transglutaminase and tyrosinase activities and activates protein kinase C. Both polar metabolites and stereoisomers of all-trans retinoic acid are also biologically active. Molecular biologic techniques have revealed that elevation of mRNA for cellular retinoic acid binding protein II is a retinoid-related event and that nuclear receptors such as retinoic acid receptors and retinoid X-receptors may transduce the retinoid response.
Griffiths
C E
CE
Department of Dermatology, Taubman Center, Ann Arbor, Michigan 48109-0314, USA.
Voorhees
J J
JJ
D002986:Clinical Trials as Topic; D006801:Humans; D012176:Retinoids / Q000378:metabolism / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects; D012871:Skin Diseases / Q000188:drug therapy / Q000378:metabolism
D012176:Retinoids