title: Retinoic acid differentially up-regulates the gene expression of retinoic acid receptor alpha and gamma 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-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.
authors.affiliation: Department of Agricultural Chemistry, Faculty of Agriculture, Tokyo University of Agriculture, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takeyama
authors.forename: R
authors.initials: R
authors.lastname: Kojima
authors.forename: R
authors.initials: R
authors.lastname: Ohashi
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Mano
authors.forename: S
authors.initials: S
authors.lastname: Masushige
authors.forename: S
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D015342:DNA Probes; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D000097768:Retinoic Acid Receptor gamma
chemical_list: D015342:DNA Probes; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C000607073:Rara protein, rat; C082925:retinoic acid receptor beta