Prolactin increases hepatic Na+/taurocholate co-transport activity and messenger RNA post partum.
We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant controls, and that activity can be increased by treatment with ovine prolactin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87]. To determine the basis for these effects, Na+/taurocholate co-transport was determined in purified basolateral liver plasma-membrane (bLPM) vesicles and compared with steady-state mRNA levels encoding the Na+/taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant controls, pregnant rats (19-20 days pregnant), rats post partum (48 h post partum) and rats post partum treated with bromocriptine to inhibit prolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s per mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregnant 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 bromocriptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0.9. Northern and slot-blot analyses revealed similar changes in mRNA for Ntcp, so that a positive correlation was observed between Na+/taurocholate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold compared with solvent-treated controls, consistent with the 2-fold increase in Vmax, for Na+/taurocholate co-transport in isolated hepatocytes. These data are the first to demonstrate endogenous physiological regulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate co-transport activity.
Ganguly
T C
TC
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington 40536.
Liu
Y
Y
Hyde
J F
JF
Hagenbuch
B
B
Meier
P J
PJ
Vore
M
M
D000818:Animals; D001692:Biological Transport; D001971:Bromocriptine / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D029363:Organic Anion Transporters, Sodium-Dependent; D049590:Postpartum Period / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011388:Prolactin / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012964:Sodium / Q000378:metabolism*; D027981:Symporters; D013656:Taurocholic Acid / Q000378:metabolism*
D002352:Carrier Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; C071908:sodium-bile acid cotransporter; D001971:Bromocriptine; D013656:Taurocholic Acid; D011388:Prolactin; D012964:Sodium