Strain- and sex-specific variations in hepatic glutamine synthetase activity and distribution in rats and mice

The distribution of glutamine synthetase (GS) in a mammalian liver is restricted to a small zone of hepatocytes surrounding the central veins. The determination of the size of the GS+ zone in rats by immunohistochemistry revealed that it differed between rat strains and was larger 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 Sprague-Dawley, Wistar, and Fischer rats, respectively. Upon orchidectomy of male rats, the size of the GS+ zone diminished towards the value found in females, while ovariectomy was without effect. This orchidectomy-induced reduction was reflected in corresponding changes of the RMW values as well as in the number of GS+ cells per pericentral field and was not due to the slightly smaller size of the GS+ hepatocytes 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 after 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 the activity of glucose-6-phosphate dehydrogenase (G6PD). The observed sex differences in the activity and distribution of GS in rat livers suggest that sex hormones not only modulate the level of this enzyme but 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.