PROLACTIN INCREASES MESSENGER-RNA ENCODING NA+-TC COTRANSPORT POLYPEPTIDE AND HEPATIC NA+-TC COTRANSPORT

We have shown that prolactin (Prl) increases the transhepatic transport of taurocholate (TC) in postpartum rats and following treatment of ovariectomized (Ovx) rats with ovine Prl (oPrl). The present studies were designed to determine if treatment of Ovx rats with oPrl (100, 300, or 600 mu g/day, 7 days iv) 1) increases Naf-TC cotransport in basolateral plasma membrane vesicles (bLPM), 2) induces a corresponding increase in the steady-state levels of Na+-TC cotransport polypeptide (Ntcp mRNA), and 3) if the oPrl-mediated increase in Na+-TC cotransport activity is blocked by cycloheximide, an inhibitor of protein synthesis. oPrl (300 mu g/day) induced a twofold increase in the maximal velocity for Na+-TC cotransport in both hepatocytes and bLPM vesicles with little change in the Michaelis constant. Infusion of oPrl at a dose of 100, 300, or 600 mu g/day increased steady-state Ntcp mRNA four-, ten-, and twofold, respectively. Finally, cycloheximide blocked the oPrl-mediated increase in Nat-TC cotransport but did not affect basal activity. These data support the hypothesis that an increase in Ntcp mRNA followed by increased synthesis and incorporation of Ntcp in the plasma membrane is responsible for the oPrl-mediated increase in Na+-TC cotransport in the basolateral plasma membrane domain of the hepatocyte.