Retinoic acid is essential for the normal differentiation of epithelia but its cellular function is obscure. The expression patterns of retinoic acid receptors (RARs) in skin cell types may give an insight into the role of retinoic acid in skin. We have compared the patterns of RAR expression in human keratinocytes and dermal fibroblasts in vitro, and studied the effects of retinoic acid on RAR expression. RAR-alpha and RAR-gamma were expressed in keratinocytes and fibroblasts: RAR-gamma was expressed at similar levels in both cell types but RAR-alpha was more abundant in fibroblasts. There were no differences in expression of either RAR-alpha or RAR-gamma between stratifying (high-calcium medium) and proliferating (low-calcium medium) keratinocytes and expression of these RARs was unaffected by retinoic acid. RAR-beta was undetectable in keratinocytes. In the majority of fibroblast cell lines, RAR-beta transcripts were either undetectable or expressed at a low level. Retinoic acid at low concentrations (10(−10) to 10(−9) M) rapidly induced the expression of RAR-beta. Cyclic adenosine monophosphate (cAMP) analogues inhibit RAR-beta induction in teratocarcinoma cells. However, dibutyryl-cAMP did not affect RAR-beta induction in fibroblasts. Forskolin, an adenylate cyclase activator, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) decreased constitutive RAR-beta mRNA levels but did not block induction of RAR-beta by retinoic acid. Since intracellular cAMP levels were only increased detectably in response to forskolin, the reduction in constitutive levels of RAR-beta mRNA may be mediated by mechanisms other than via cAMP.

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