Metallothionein (MT) and glutathione (GSH) have been implicated as two
major copper-binding agents involved in the hepatobiliary copper meta
bolism in the adult rat, This study was designed to explore their pote
ntial role in facilitating copper export from the copper-laden hepatoc
yte of the newborn rat, Biliary and hepatic copper, GSH, and immunorea
ctive MT-I concentrations were measured in Sprague-Dawley rats at 1, 2
, 3, 4, and 8 weeks of age, Bile was collected by duct cannulation for
90 minutes before the rats were killed. Liver was removed, weighed, a
nd freeze-dried, The bile flow rate (BFR) doubled and the Liver weight
increased 14-fold during maturation. Hepatic and biliary copper and M
T-I concentrations were significantly higher in the suckling than in t
he weanling, The total biliary output of copper per 24 hours was low a
t 1 week and increased significantly by 8 weeks of age, MT-I-bound cop
per represented a maximum of only 3.4% of biliary copper at I week and
0.5% at 8 weeks. GSH was not detected in bile until 2 weeks and then
increased 15-fold by 8 weeks, while hepatic GSH levels remained unchan
ged, Therefore, GSH levels did not correlate with the high biliary cop
per concentration at week 1, although there was a close correlation be
tween the total daily biliary excretion of copper and GSH at 2 weeks a
nd beyond. We conclude that the net biliary copper excretion per day i
s relatively low in the first week of life and is independent of MI an
d GSH secretion. It increases significantly once GSH is available in b
ile, We speculate that biliary copper excretion in the neonatal rat ma
y involve copper binding agents as yet unidentified.