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Human skin exhibits a characteristic, pleiotypic response to topical retinoic acid. In attempting to understand this response at the molecular level, we have used fast protein liquid chromatography (FPLC) and RNA blot hybridization to characterize the expression of the nuclear retinoic acid receptor (RAR) alpha, beta, and γ genes in adult human epidermis. Size exclusion FPLC of 0.6 M NaCI nuclear extracts prepared from keratome biopsies revealed two peaks of specific [³H] retinoic acid (RA) binding at Mr 45 and 18 kDa, in agreement with the expected sizes of RAR and cellular RA binding protein. Blot hybridization analysis of total RNA extracted from keratome biopsies revealed that RAR-γ was the predominant RAR species expressed in human epidermis, as RAR-α transcripts were detectable only at low levels and RAR-β transcripts were undetectable. RAR transcripts were not induced by topical treatment with 0.1% RA cream under occlusion for 4 h or 4 d. Moreover, there was no significant difference in RAR-γ transcript levels in normal and psoriatic epidermis. RAR-γ transcripts were constitutively expressed not only in cultured human keratinocytes, but also in human dermal and lung fibroblasts. RAR-β was induced by RA in dermal fibroblasts, but not in keratinocytes. RA induced IL-1β transcripts in keratinocytes rapidly (2 to 4 h) and at low concentrations (3 × 10-10 M), consistent with activation of the IL-1β gene via RAR. These results demonstrate constitutive expression of RAR-γ in human epidermis, and suggest that RAR-γ is a molecular target of RA action in adult human skin. [ABSTRACT FROM AUTHOR]