Rapid corticosterone-induced changes in gene expression in rat hippocampus display type II glucocorticoid receptor specificity.

Corticosteroids influence a wide range of neuronal activities by binding to either of two different glucocorticoid receptors found in rat brain. To investigate genomic responses in brain to stress levels of circulating corticosterone (CORT), we isolated hippocampal total RNA and poly(A)-containing RNA from rats treated with 10 mg/day CORT or vehicle. RNA translation products were resolved by 2-dimensional gel electrophoresis and fluorography. Select changes in four translation products after acute CORT treatment were inferred from up to 100-fold increases in three polypeptides and a 2-fold decrease in another. While adrenalectomy decreased levels of the inducible RNA sequences (adrenalectomized vs. intact controls), CORT increased the inducible sequences above their levels in intact controls. Rapid increases within 2 h of CORT treatment were seen for RNAs coding for 35, 33, and 20 kilodalton polypeptides. However, RNA coding for a 50 kilodalton polypeptide had a delayed decrease, first seen after 32 h CORT. The CORT increases displayed type II glucocorticoid receptor-specificity: RU 28362 greater than or equal to CORT greater than aldosterone greater than dihydrotestosterone = control. Since type II receptors are only substantially occupied by stress levels of CORT, these changes in gene expression are candidates for molecular stress responses in the brain.

[1]  D. Housman,et al.  Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. , 1987, Science.

[2]  J. Reul,et al.  Differential response of type I and type II corticosteroid receptors to changes in plasma steroid level and circadian rhythmicity. , 1987, Neuroendocrinology.

[3]  R. Axel,et al.  Glucocorticoids enhance stability of human growth hormone mRNA , 1987, Molecular and cellular biology.

[4]  G. Lynch,et al.  Induction of ornithine decarboxylase as a possible mediator of seizure- elicited changes in genomic expression in rat hippocampus , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  B. McEwen,et al.  Adrenal steroid receptors and actions in the nervous system. , 1986, Physiological reviews.

[6]  M. Schlesinger.  Heat shock proteins: the search for functions , 1986, The Journal of cell biology.

[7]  G. Dienel,et al.  Synthesis of Heat Shock Proteins in Rat Brain Cortex after Transient Ischemia , 1986, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  B. McEwen,et al.  The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. , 1986, Endocrine reviews.

[9]  A. Goldberg,et al.  Abnormal proteins serve as eukaryotic stress signals and trigger the activation of heat shock genes. , 1986, Science.

[10]  E. R. Kloet,et al.  Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. , 1985, Endocrinology.

[11]  J. Meyer.  Biochemical effects of corticosteroids on neural tissues. , 1985, Physiological reviews.

[12]  R. Sapolsky,et al.  Glucocorticoids potentiate ischemic injury to neurons: therapeutic implications. , 1985, Science.

[13]  B. McEwen,et al.  Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  U. Bond,et al.  Ubiquitin is a heat shock protein in chicken embryo fibroblasts , 1985, Molecular and cellular biology.

[15]  W. Welch.  Phorbol ester, calcium ionophore, or serum added to quiescent rat embryo fibroblast cells all result in the elevated phosphorylation of two 28,000-dalton mammalian stress proteins. , 1985, The Journal of biological chemistry.

[16]  H. Goodman,et al.  Regulation of growth hormone messenger RNA synthesis by dexamethasone and triiodothyronine. Transcriptional rate and mRNA stability changes in pituitary tumor cells. , 1985, Journal of molecular biology.

[17]  D. Jacobowitz,et al.  Two-dimensional gel electrophoresis used in neurobiological studies of proteins in discrete areas of the rat brain. , 1984, Clinical chemistry.

[18]  E. Maytin,et al.  Separate glucocorticoid, heavy metal, and heat shock domains in thymic lymphocytes. , 1983, The Journal of biological chemistry.

[19]  A. Patel,et al.  Regulation of in vivo glutamine synthetase activity by glucocorticoids in the developing rat brain. , 1983, Brain research.

[20]  M. Cousin,et al.  Glucocorticoids modulate the response of ornithine decarboxylase to unilateral removal of the dorsal hippocampus , 1983, Brain Research.

[21]  R. Rosenberg,et al.  Specific messenger RNA changes in joseph disease cerebella , 1983, Annals of neurology.

[22]  G. Kovacs,et al.  Aldosterone blocks the response to corticosterone in the raphe-hippocampal serotonin system , 1983, Brain Research.

[23]  M. Cousin,et al.  Ornithine Decarboxylase Induction by Glucocorticoids in Brain and Liver of Adrenalectomized Rats , 1982, Journal of neurochemistry.

[24]  G. Teutsch,et al.  17α-Alkynyl-11β,17-dihydroxyandrostane derivatives : A new class of potent glucocorticoids. , 1981, Steroids.

[25]  W. Meyer,et al.  Mineralocorticoid binding in cultured smooth muscle cells and fibroblasts from rat aorta. , 1981, Journal of steroid biochemistry.

[26]  D. Young,et al.  Cellular and biochemical actions of adrenal glucocorticoid hormones on rat thymic lymphocytes. , 1981, Environmental health perspectives.

[27]  G. Lynch,et al.  Characterization of Corticosterone‐Induced Protein Synthesis in Hippocampal Slices , 1980, Journal of neurochemistry.

[28]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[29]  S. Bernstein,et al.  An improved method for the rapid isolation of brain ribonucleic acid. , 1979, The Biochemical journal.

[30]  G. Lynch,et al.  Hippocampal aging and adrenocorticoids: quantitative correlations. , 1978, Science.

[31]  F. Amalric,et al.  Fractionation of mitochondrial RNA from HeLa cells by high-resolution electrophoresis under strongly denaturing conditions. , 1978, Journal of molecular biology.

[32]  R. Laskey,et al.  Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. , 1975, European journal of biochemistry.

[33]  P. O’Farrell.  High resolution two-dimensional electrophoresis of proteins. , 1975, The Journal of biological chemistry.

[34]  W. Bonner,et al.  A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. , 1974, European journal of biochemistry.

[35]  J. Funder,et al.  Adrenocortical steroids and the brain. , 1987, Annual review of physiology.

[36]  H. Pelham.  Activation of heat-shock genes in eukaryotes , 1985 .

[37]  C. Cotman,et al.  Elevated corticosterone levels. A possible cause of reduced axon sprouting in aged animals. , 1984, Neuroendocrinology.

[38]  N. Holbrook,et al.  Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. , 1984, Endocrine reviews.

[39]  E. R. Kloet.  Adrenal steroids as modulators of nerve cell function. , 1984 .

[40]  M. Dallman,et al.  Corticosteroid inhibition of ACTH secretion. , 1984, Endocrine reviews.