Retinoic acid and dexamethasone interact to regulate S14 gene transcription in 3T3-F442A adipocytes.

We have examined the effects of retinoic acid (RA) on S14 gene expression in 3T3-F442A preadipocytes and adipocytes. RA induced mRNAS14 14-fold in adipocytes, but had no effect on S14 gene expression in preadipocytes. Northern analysis of retinoic acid receptor (RAR) isoforms revealed the presence of RAR alpha, but not RAR beta, in both preadipocytes and adipocytes. These results suggest that adipocyte-specific factors expressed during differentiation may be required for RA control of S14 gene expression in cultured adipocytes. When compared to dexamethasone (DEX), RA was a weak inducer of S14 gene expression. However, when added together, RA and DEX acted synergistically to induce S14 gene expression. Since changes in S14 gene transcription paralleled changes in mRNAS14 levels, the principal target for RA and DEX action on S14 gene expression was at the level of gene transcription. In the presence of DEX (0.1 nM), RA effects on S14 gene expression were dose-dependent (ED50 = 5 nM) and rapid (within 4 h). In contrast to S14, RA inhibited glycerol 3-phosphate dehydrogenase (GPD) gene transcription and mRNAGDP abundance by 75%. The effects of RA on S14 and GPD gene transcription in cultured adipocytes suggest that RA action may extend beyond growth and differentiation to include effects on lipid metabolism.