Steroids, Stress, and Gene Expression in Neurons.

摘要

In order to identify glucocorticoid responses that mediate cellular adaptation to stress, we have examined changes in gene expression in rat hippocampus in response to acute corticosterone (CORT) treatment or to vibratory stress. Previously, we described select changes in four poly(A)- containing RNAs, coding for 50, 35, 33 and 20 kd polypeptides, in response to administered CORT. We have cloned five CORT-responsive mRNAs from a rat hippocampal cDNA library by differential hybridization and compared them to the previous responses by hybrid selection, in vitro translation, and 2-d gel analysis. Two of the clones hybridized to mRNAs coding for the 50 and 35 kd polypeptides; they were identified from partial DNA sequences as glial fibrillary acidic protein and glycerol phosphate dehydrogenase. Another clone was identified as glutamine synthetase and two were not identified, CR16 and CR62. CORT and stress responsiveness of these mRNAs were compared by 2-d gel analysis of in vitro translation products or RNA hybridization experiments. Only GPDH/35 kd and 20 kd were responsive to 2 hr CORT treatment and 2 hr vibratory stress. The lack of response to stress of the other mRNAs, despite elevated CORT levels, is consistent with their slower response to exogenous CORT. We find subsets of mRNA responses which differ in temporal and other aspects of CORT regulation. Examining a variety of stressors and chronic stress will determine if this is a general or unique pattern of expression of CORT-dependent responses in hippocampus. (kt)