PROLACTIN INCREASES HEPATIC NA+ TAUROCHOLATE COTRANSPORT ACTIVITY ANDMESSENGER-RNA POST-PARTUM/

We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant contr ols, and that activity can be increased by treatment with ovine prolac tin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87 ]. To determine the basis for these effects, Na+/taurocholate co-trans port was determined in purified basolateral liver plasma-membrane (bLP M) vesicles and compared with steady-state mRNA levels encoding the Na +/ taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant con trols, pregnant rats (19-20 days pregnant), rats post partum (48 h pos t partum) and rats post partum treated with bromocryptine to inhibit p rolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s p er mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregn ant controls to 7.9 +/- 0.6 in bLPM in pregnant rats, but rebounded to 17.5 +/- 1.3 post partum; treatment of rats post partum with bromocry ptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0. 9. Northern and slot-blot analyses revealed similar changes in mRNA fo r Ntcp, so that a positive correlation was observed between Na+/tauroc holate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold c ompared with solvent-treated controls, consistent with the 2-fold incr ease in V-max for Na+/taurocholate co-transport in isolated hepatocyte s. These data are the first to demonstrate endogenous physiological re gulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate c o-transport activity.