Gtm. Wagenaar et al., DISTRIBUTION AND ACTIVITY OF GLUTAMINE SYNTHASE AND CARBAMOYLPHOSPHATE SYNTHASE UPON ENLARGEMENT OF THE LIVER LOBULE BY REPEATED PARTIAL HEPATECTOMIES, Journal of hepatology, 17(3), 1993, pp. 397-407
Glutamine synthase and carbamoylphosphate synthase show a strikingly h
eterogeneous and fully complementary distribution in the rat liver. In
the human liver, however, there is a midlobular zone where both enzym
es are absent. The diameter of the human liver lobule is approximately
twice the size of the rat lobule. To investigate whether lobule size
is a major determinant for the expression patterns of glutamine syntha
se and carbamoylphosphate synthase, Wistar strain rats were partially
hepatectomized 3 times, at weekly or monthly intervals. Due to hepatic
regeneration the cross-sectional area of the liver lobules increased
twofold. However, a midlobular zone which lacked expression of both gl
utamine synthase and carbamoylphosphate synthase did not develop in th
ese livers, thus showing that lobular size is not a major determinant
for the distribution patterns of glutamine and carbamoylphosphate synt
hase. The twofold increase in the cross-sectional area of the liver lo
bule was associated with a similar reduction in the relative number of
glutamine synthase-positive cells and in the enzyme content of the li
ver, indicating that the regeneration process does not affect the peri
central pattern of glutamine synthase expression. After regeneration w
as complete, the glutamine synthase content in the liver was restored
to its original value, demonstrating a twofold increase in the cellula
r concentration of glutamine synthase-positive hepatocytes. An increas
e in the diameter of the liver lobule was only seen after the first pa
rtial hepatectomy. Liver growth following subsequent partial hepatecto
mies can be explained by an increase in the length of the liver lobule
and/or by splitting of liver lobules. The zona distribution of DNA re
plication, which is characteristic of the first partial hepatectomy, i
s lost after repeated partial hepatectomies. Furthermore, evidence was
obtained that the signal for inducing DNA synthesis may originate at
the level of single liver units.