RETINOIC ACID DIFFERENTIALLY UP-REGULATES THE GENE-EXPRESSION OF RETINOIC ACID RECEPTOR-ALPHA AND RECEPTOR-GAMMA ISOFORMS IN EMBRYO AND ADULT-RATS

The diverse biological effects of retinoic acid (RA) are exerted by it s nuclear receptor-mediated gene expression. One of the two nuclear re tinoic acid receptor subfamilies is composed of three subtypes of the all-trans retinoic acid receptor (RAR-alpha, RAR-beta, and RAR-gamma). Furthermore, several isoforms are generated from each of three RARs b y differential promoter usage and/or alternative splicing. It is thus thought that the developmental stage-specific actions of RA are modula ted 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 isofo rms (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 emb ryo and maternal tissues by administering pregnant rats with an excess of all-trans RA. The expression of RAR-beta isoforms as well as the R AR-beta total was auto-regulated by RA in all maternal tissues and emb ryos examined. The gene expression of RAR-alpha 2, which was not affec ted by RA in the maternal tissues, was up-regulated in embryos, though there were no significant effects of KA 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 onl y in the maternal tissues. Thus, these results indicates that two reti noic acid receptor isoforms (RAR-alpha 2 and RAR-gamma 2) are differen tially auto-regulated in embryo and adult rats. (C) 1996 Academic Pres s, Inc.