Retinoic acid differentially up-regulates the gene expression of retinoic acid receptor alpha and gamma isoforms in embryo and adult rats.

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-transretinoic acid receptor (RAR-alpha, RAR-beta, and RAR-gamma). 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-alpha total, RAR-beta total and RAR-gamma total) and their major isoforms (RAR-alpha 1, alpha 2, RAR-beta 1, beta 2 and RAR-gamma 1, gamma 2) 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-beta isoforms as well as the RAR-beta total was auto-regulated by RA in all maternal tissues and embryos examined. The gene expression of RAR-alpha 2, 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-alpha 1 and the alpha total in the maternal tissues and the embryos. Likewise, RA did not affect the levels of RAR-gamma 1 and gamma total. However, unlike RAR-alpha 2, RAR-gamma 2 expression was up-regulated by RA only in the maternal tissues. Thus, these results indicates that two retinoic acid receptor isoforms (RAR-alpha 2 and RAR-gamma 2) are differentially auto-regulated in embryo and adult rats.