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Differential regulation of hepatic bile salt and organic anion transporters in pregnant and postpartum rats and the role of prolactin
Author(s) -
Cao Jingsong,
Huang Liyue,
Liu Yong,
Hoffman Tim,
Stieger Bruno,
Meier Peter J.,
Vore Mary
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.20895
Subject(s) - multidrug resistance associated protein 2 , endocrinology , prolactin , medicine , organic anion transporter 1 , bile salt export pump , symporter , prolactin receptor , organic anion transporting polypeptide , postpartum period , messenger rna , chemistry , pregnancy , biology , transporter , hormone , biochemistry , atp binding cassette transporter , genetics , gene
We characterized expression and activity of the bile salt transporters Na + /taurocholate (TC) cotransporting polypeptide (Ntcp), and bile salt export pump (Bsep), and the expression of organic anion transporting polypeptides 1 and 2 (Oatp1 and 2) and multidrug resistance associated protein‐2 (Mrp2) in pregnancy and throughout lactation in rats. The V max for Na + /TC cotransport in basolateral liver plasma membrane was increased 1.7‐fold in 2 days postpartum relative to control and pregnant rats. This correlated well with an increase in Ntcp messenger RNA (mRNA) and a 2‐fold increase in Ntcp protein. Ntcp mRNA remained significantly elevated until 14 days postpartum but had begun to decline by 21 days postpartum. The maximal secretory rate (nmol/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 correlated with increased expression of Ntcp and Bsep mRNA and protein. Infusion of ovine prolactin (oPRL) to ovariectomized rats increased expression of both Ntcp and Bsep mRNA and protein. These data indicate a coordinate increased expression of bile salt transporters postpartum and by PRL. Mrp2 mRNA was stable in pregnancy and postpartum, whereas Mrp2 protein expression decreased significantly in pregnancy, but returned to control levels postpartum. Organic anion transporting polypeptide 2 (Oatp2) mRNA was decreased in pregnancy and increased postpartum, but changes in Oatp2 protein were not significant. Oatp1 mRNA and protein were unchanged in pregnancy and postpartum.