title: In vivo isomerization of retinoic acids. Rapid isomer exchange and gene expression.
abstract: The in vivo isomerization of all-trans- and 9-cis-retinoic acids (RAs) was evaluated by high performance liquid chromatography after oral administration to rats. All-trans (2 ng/ml)- and 13-cis (1.8 ng/ml)-RAs, but not 9-cis-RA, were detected in the serum of normal rats. When an excess of either all-trans-RA or 9-cis-RA (100 micrograms/rat) was intragastrically administered to the retinoid-depleted rats, a rapid isomer exchange between 9-cis- and all-trans-RAs along with appearance of the administered RA occurred shortly after the dose (30 min). RA rapidly isomerized when an excess of either all-trans- or 9-cis-RA (1 mg/rat) was administered to normal rats. To examine whether the isomerized RAs elicit biological actions in vivo, the induction of target genes-[cellular retinol-binding protein type II (CRBP II) for 9-cis-RA and all-trans-retinoic acid receptor beta (RAR beta) for 9-cis- and all-trans-RAs] was determined. The degree of induction of the two genes did not differ 4 h after administration of either 9-cis-RA or all-trans-RA. However, unlike all-trans-RA, the RAR-specific synthetic retinoids did not induce the CRBP II gene. These results suggested that the apparent actions of 9-cis- and all-trans-RAs on gene expression in vivo may be mediated to some extent by the converted stereoisomer.
authors.affiliation: Department of Agricultural Chemistry, Faculty of Agriculture, Tokyo University of Agriculture, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Fujimori
authors.forename: N
authors.initials: N
authors.lastname: Kiyota
authors.forename: Y
authors.initials: Y
authors.lastname: Toriya
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Ohashi
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshizawa
authors.forename: K
authors.initials: K
authors.lastname: Takeyama
authors.forename: H
authors.initials: H
authors.lastname: Mano
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015870:Gene Expression; D007536:Isomerism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000235:genetics; D014212:Tretinoin / Q000097:blood / Q000378:metabolism*
chemical_list: D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin