Retinoic Acid Differentially Up-Regulates the Gene Expression of Retinoic Acid Receptor α and γ Isoforms in Embryo and Adult Rats

Abstract

The diverse biological effects of retinoic acid (RA) are exerted by its nuclear receptor-mediated gene expression. One of the two nuclear retinoic acid receptor subfamilies is composed of three subtypes of the all-trans retinoic acid receptor (RAR-α,RAR-β,and RAR-γ). Furthermore, several isoforms are generated from each of three RARs by differential promoter usage and/or alternative splicing. It is thus thought that the developmental stage-specific actions of RA are modulated through the spatio-temporal expression of the subtype and isoforms of RARs. In this study, the auto-regulation of the RAR subtypes (RAR-α total, RAR-β total and RAR-γ total) and their major isoforms (RAR-α1, α2, RAR-β1, β2 and RAR-γ1, γ2) by RA was examined by means of Northern blotting in the 11.5 day embryo and maternal tissues by administering pregnant rats with an excess of all-trans RA. The expression of RAR-β isoforms as well as the RAR-β total was auto-regulated by RA in all maternal tissues and embryos examined. The gene expression of RAR-α2, which was not affected by RA in the maternal tissues, was up-regulated in embryos, though there were no significant effects of RA on the levels of RAR-α1 and the α total in the maternal tissues and the embryos. Likewise, RA did not affect the levels of RAR-γ1 and γ total. However, unlike RAR-α2, RAR-γ2 expression was up-regulated by RA only in the maternal tissues. Thus, these results indicates that two retinoic acid receptor isoforms (RAR-α2 and RAR-γ2) are differentially auto-regulated in embryo and adult rats.