H. Sirma et al., STRAIN-SPECIFIC AND SEX-SPECIFIC VARIATIONS IN HEPATIC GLUTAMINE-SYNTHETASE ACTIVITY AND DISTRIBUTION IN RATS AND MICE, Liver, 16(3), 1996, pp. 166-173
The distribution of glutamine synthetase (GS) in a mammalian liver is
restricted to a small zone of hepatocytes surrounding the central vein
s. The determination of the size of the GS(+) zone in rats by immunohi
stochemistry revealed that it differed between rat strains and was lar
ger in males than in females of each strain. Accordingly the means of
the relative mean width (RMW) values that characterize the size of the
GS(+) zone were 19%, 26%, and 39% lower in females than in males of S
prague-Dawley, Wistar, and Fischer rats, respectively. Upon orchidecto
my of male rats, the size of the GS(+) zone diminished towards the val
ue found in females, while ovariectomy was without effect. This orchid
ectomy-induced reduction was reflected in corresponding changes of the
RMW values as well as in the number of GS(+) cells per pericentral fi
eld and was not due to the slightly smaller size of the GS(+) hepatocy
tes in the orchidectomized males. No such sex difference was found in
M775 mice. Biochemical GS activity was higher in the male rats than in
the female rats and changed correspondingly to the distribution after
gonadectomy. In the mice, only the specific activity of GS dropped af
ter orchidectomy. In primary cultures of rat hepatocytes, no influence
of testosterone or estrogen on GS activity and cellular distribution
was observed, even after stimulation of GS activity with dexamethasone
and growth hormone. Both sex hormones, however, were able to affect t
he activity of glucose-6-phosphate dehydrogenase (G6PD). The observed
sex differences in the activity and distribution of GS in rat livers s
uggest that sex hormones not only modulate the level of this enzyme bu
t are at least partially involved in the determination of the size of
the compartment of GS expression. According to the results in the cell
cultures, the effects of the sex hormones appear indirect rather than
direct.