Regulation of in vivo glutamine synthetase activity by glucocorticoids in the developing rat brain

Induction of glutamine synthetase in vivo by glucocorticoids was studied in different brain regions of the rat during development. Corticosterone treatment resulted in an age-dependent increase in glutamine synthetase activity. In 11-day-old rats, in comparison with controls, the increase was about 80% in the cerebellum, 50% in the olfactory bulbs and 20% in the forebrain. During development the effect diminished markedly and at day 20 a marked increase was detectable only in the cerebellum, suggesting that the elevation of glutamine synthetase was dependent on the maturational state of the region at the time of hormone treatment. The increase in enzyme activity was dose-dependent, and was also observed after treatment with dexamethasone but not with testosterone, estradiol or progesterone. Pre-treatment with the protein synthesis inhibitor anisomycin blocked the hormonal response. Also, immunochemical detection of glutamine synthetase in brain homogenates fractionated by SDS-polyacrylamide gel electrophoresis and transferred to diazobenzyloxymethyl paper showed that the increase in enzyme activity was due to induction of protein synthesis. This may be the first report showing a regulation by glucocorticoids of mammalian brain glutamine synthetase in vivo, and it is in good agreement with previous findings with chick retina in vivo and various avian and mammalian cells in vitro.