|Reinhardt, Timothy - Tim|
Submitted to: Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/27/1995
Publication Date: N/A
Citation: Interpretive Summary: Vitamin A is known to play a critical role in maintenance of biological processes including the movement of calcium into and out of the bone and maintenance of normal immune function. In order to carry out these functions, vitamin A must be "activated." The active form of vitamin A is retinoic acid. Retinoic acid occurs naturally in several forms called "isomers." Each isomer has unique activities and possibly unique functions. In this report, we described a new assay which identified one of these isomers as the major circulating retinoic acid in plasma of dairy cattle during late pregnancy and early lactation. This is a period of time when the cow's immune system is not functioning properly, and also a period of time when cattle are suffering from calcium deficits due to the sudden need for calcium to support milk production. The chemical name for this isomer is 9,13-di-cis-retinoic acid. This form of retinoic acid could not be found in human or rat plasma during late pregnancy or early lactation. Due to its relative abundance in the cow, we are currently testing this isomer to determine if it has a role in modifying the activity of cells which play a role in immunity and/or those responsible for regulating changes in body calcium.
Technical Abstract: This study examined changes in the geometric isomers of retinoic acid (RA) during late gestation and early lactation in the dairy cow. Blood samples were collected for from 14 days pre-partum and continuing to 14 days post-partum. Assays were done conventionally using solid phase extraction followed by quantitation of RA isomers by reverse-phase high pressure liquid chromatography (HPLC). The major RA in plasma of periparturient cows was 9,13-di-cis-RA. 9,13-Di-cis-RA was present at approx. 1 ng/mL 10 days prior to parturition, and was elevated to approx. 2 ng/mL by 1 day pre-partum; then rapidly raised to >4 ng/mL by 1 day post-partum. 9,13-Di-cis-RA remained elevated (approx. 4 ng/mL) for at least 14 days post-partum. Plasma all-trans-RA, 13-cis-RA, and 9-cis- RA were also elevated during the periparturient period with the most pronounced changes (approx. 25-30% increase) occurring between the day of parturition to 4 days post-partum. 9,13-Di-cis-RA was 116- and 30-fold less competitive than 9-cis-RA for binding to retinoid X receptor (RXR) alpha and RXR beta, 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 cis-RA. This study establishes that profound changes in vitamin A metabolism occur in late gestation and early lactation in the bovine.