Following treatment of rats with a subcutaneous injection of 5 mg of corticosterone, hippocampal slices in vitro show increased labeling from 35S-methionine of a protein with an apparent molecular weight (Mr) of 35,000. Increased protein labeling is seen in response to corticosterone, dexamethasone, and aldosterone, steroids that associate with glucocorticoid receptors. Little or no response occurs after administration of progesterone or estradiol. Because the injected dose of steroids is high and responses to an injection of this magnitude may be pharmacological, several experiments have been done to determine whether stimuli that increase endogenous levels of corticosterone have the same effect on labeling of the 35,000 Mr protein. One hour after various stresses (immobilization, cold, ether, and sham-injection), when plasma levels of corticosterone are elevated, labeling of the 35,000 Mr protein is increased. Injection of ACTH also stimulates the synthesis of this protein in intact animals in a manner analogous to that seen with corticosterone injections. In addition, a dose-response curve for corticosterone with adrenalectomized rats shows that synthesis of the protein is maximally increased when the injected dosage causes serum levels of corticosterone to increase to the levels seen during stress. The increase in labeling of the 35,000 Mr protein in adrenalectomized animals is only half as great as that observed in intact animals. Injections of the type II glucocorticoid (GR) receptor agonist, RU 28362, into adrenalectomized rats differentially stimulates the synthesis of the 35,000 Mr protein compared with the mineralocorticoid aldosterone, which has a higher affinity for the type I (CR) receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Previously, the synthesis of a hippocampal 35,000 M(r) protein increased in response to glucocorticoid treatment and a variety of stressors. We now show by immunoprecipitation that this cytosolic protein is glycerol 3-phosphate dehydrogenase (E.C.1.1.1.8; GPDH). In addition, four polypeptides encoded by glucocorticoid-induced mRNAs co-migrated with hippocampal protein synthetic products on two-dimensional polyacrylamide gels, including 35,000 M(r) protein of approximately pl 6.3, that had previously been identified as GPDH by hybrid-selection with a GPDH cDNA clone. The 35,000 M(r) in vitro translation product was also immunoprecipitated with the GPDH antibody. Using radiolabeled hippocampal slices and two-dimensional gel analysis, a 35,000 M(r) polypeptide of approximately pl 6.4 increased five-fold after 30 min of intermittent tail-shock. This protein was found predominantly in the 20,000 x g pellet and did not immunoprecipitate with the GPDH antibody. However, a 35,000 M(r) polypeptide was also found in the cytosol as a minor component after stress, which did immunoprecipitate with the GPDH antibody. Therefore, there are at least two shock-induced 35,000 M(r) proteins, one of which is GPDH. These results establish that increases in GPDH mRNA prevalence and protein synthesis occur in response to both glucocorticoids and stress in the adult rat hippocampus. Based on the increased enzyme activity seen in the nervous system in response to glucocorticoids, dietary restriction, and nerve injury, the induction of GPDH may have functional consequences in cellular adaptation to stress.