In vivo isomerization of retinoic acids. Rapid isomer exchange and gene expression.
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.
Kojima
R
R
Department of Agricultural Chemistry, Faculty of Agriculture, Tokyo University of Agriculture, Japan.
Fujimori
T
T
Kiyota
N
N
Toriya
Y
Y
Fukuda
T
T
Ohashi
T
T
Sato
T
T
Yoshizawa
Y
Y
Takeyama
K
K
Mano
H
H
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*
D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin