Differential regulation of hepatic bile salt and organic anion transporters in pregnant and postpartum rats and the role of prolactin

We characterized expression and activity of the bile salt transporters Na+/ taurocholate (TC) cotransporting polypeptide (Ntcp), and bile salt export p ump (Bsep), and the expression of organic anion transporting polypeptides 1 and 2 (Oatp1 and 2) and multidrug resistance associated protein-2 (Mrp2) i n pregnancy and throughout lactation in rats. The V-max for Na+/TC cotransp ort in basolateral liver plasma membrane was increased 1.7-fold in 2 days p ostpartum relative to control and pregnant rats. This correlated well with an increase in Ntcp messenger RNA (mRNA) and a 2-fold increase in Ntcp prot ein. Ntcp mRNA remained significantly elevated until 14 days postpartum but had begun to decline by 21 days postpartum. The maximal secretory rate (nm ol/min/g liver) for TC in the single pass isolated perfused liver was also increased by 10%, 31%, and 24% at 2, 14, and 21 days postpartum and correla ted with increased expression of Ntcp and Bsep mRNA and protein. Infusion o f ovine prolactin (oPRL) to ovariectomized rats increased expression of bot h Ntcp and Bsep mRNA and protein. These data indicate a coordinate increase d expression of bile salt transporters postpartum and by PRL, Mrp2 mRNA was stable in pregnancy and postpartum, whereas Mrp2 protein expression decrea sed significantly in pregnancy, but returned to control levels postpartum, Organic anion transporting polypeptide 2 (Oatp2) mRNA was decreased in preg nancy and increased postpartum, but changes in Oatp2 protein were not signi ficant. Oatp1 mRNA and protein were unchanged in pregnancy and postpartum.