9,13-Di- cis-Retinoic Acid Is the Major Circulating Geometric Isomer of Retinoic Acid in the Periparturient Period

Abstract

This study examines changes in the geometric isomers of retinoic acid (RA) during late gestation and early lactation. Blood samples were collected from dairy cows at 14 days prepartum and continuing until 14 days postpartum. Assays were done using solid-phase extraction followed by quantitation of RA isomers by reverse-phase HPLC. The major RA in plasma of periparturient cows was 9,13-di- cis-RA. 9,13-Di- cis-RA was present at ≤ 1 ng/ml 10 days prior to parturition and was elevated to ∼2 ng/ml by 1 day prepartum, then increased to >4 ng/ml by 1 day postpartum. 9,13-Di- cis-RA remained at ∼4 ng/ml for at least 14 days postpartum. Plasma all- trans-RA, 13- cis-RA, and 9 cis-RA were also elevated during the periparturient period with the most pronounced changes (∼25-30% increase) occurring between the day of parturition and 4 days postpartum. 9,13-Di- cis-RA was 116- and 30-fold less competitive than 9- cis-RA for binding to human retinoid X receptors (hRXR)α and hRXRβ, respectively. Because of this relatively low affinity for the RXR, it seems that 9,13-di- cis-RA per se would contribute marginally, if at all, to the pleiotropic effects attributed to 9- cis-RA. This study establishes that profound changes in vitamin A metabolism occur in late gestation and early lactation. Because 9,13-di- cis-RA is a metabolite of 9- cis-RA, these data imply that there are dramatic fluctuations in 9- cis-RA which are more profound than other physiologically occurring RAs, particularly all- trans-RA.