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      Neurotransmitter modulation of glucocorticoid receptor mRNA levels in the rat hippocampus.

      1 , , ,
      Neuroendocrinology
      S. Karger AG

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          Abstract

          Glucocorticoids in the hippocampus mediate adaptive responses elicited by stressful stimuli. In this study we investigated glucocorticoid receptor gene expression in the rat hippocampus following acute stress. A significant decrease in glucocorticoid receptor mRNA levels was observed in the hippocampus less than 1 h after the onset of stress. This decrease was inhibited by administering either MK-801, diazepam or propranolol prior to exposure to stress. The effect of diazepam on the stress-induced decrease in hippocampal glucocorticoid receptor mRNA was reversed by Ro-15-1788, suggesting that it is mediated by central benzodiazepine receptors, i.e. GABA-A. These results indicate that NMDA, GABA-A and beta-adrenergic receptors are involved in the mechanism of the stress-induced decrease in glucocorticoid receptor mRNA levels in the rat hippocampus.

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          Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA.

          We isolated and sequenced 6.3 kb of cDNA encoding that rat glucocorticoid receptor, a protein that binds and activates a class of hormone-dependent transcriptional enhancers. Receptor-containing cells produce receptor mRNAs of approximately equal to 6.5 kb and approximately equal to 4.8 kb that differ only in their 3' nontranslated regions; an open reading frame of 795 amino acids resides within the 5' portion of the transcripts. The coding region was expressed in vitro, in transient transfections, and in stable transfectants of a receptor-deficient cell line. The protein products are indistinguishable from bona fide receptor with respect to sedimentation and electrophoretic mobility, antibody reactivity, and hormone and DNA binding. Moreover, the cloned receptor protein activates its corresponding enhancers, restoring to the receptor-deficient cells the full capacity for regulated enhancement.
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            Central 6-hydroxydopamine lesions decrease mineralocorticoid, but not glucocorticoid receptor gene expression in the rat hippocampus

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              Homolateral cerebrocortical increase of immediate early gene and neurotransmitter messenger RNAs after minimal cortical lesion: blockade by N-methyl-D-aspartate antagonist.

              A small surgical lesion of the parietal cortex induces an increase in the expression of several messenger RNAs varying from 172 to 980% in the entire homolateral cerebral cortex, as detected by quantitative in situ hybridization histochemistry. The messenger RNAs encoding the immediate early genes of the leucine zipper family (c-fos, c-jun, jun-B), the Zinc finger family (zif268), the glucocorticoid receptor family (NGFI-B) and the interferon family (PC4) are increased within 2 h after the lesion and return to normal levels at 6 h. The messenger RNAs encoding cholecystokinin, neuropeptide Y, somatostatin and the synthetizing enzyme of the neurotransmitter GABA, glutamate decarboxylase, are elevated within one day and return to normal levels after six days. An intraperitoneal injection of the N-methyl-D-aspartate receptor antagonist dizocilpine maleate, 30 min before surgery, prevented either the induction of immediate early gene expression or the increase of neuropeptide and glutamate decarboxylase messenger RNA expression. This study demonstrates that a minimal cortical lesion induces extensive changes in gene expression and that the mechanism(s) leading to these changes involves the action of glutamate at the N-methyl-D-aspartate receptor. These modifications may be of importance in explaining diffuse changes not related to neuronal circuitry in several conditions.
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                Author and article information

                Journal
                Neuroendocrinology
                Neuroendocrinology
                S. Karger AG
                0028-3835
                0028-3835
                May 1999
                : 69
                : 5
                Affiliations
                [1 ] Laboratory of Biology-Biochemistry, Faculty of Nursing, Medical School, University of Athens, Greece.
                Article
                54434
                10.1159/000054434
                10343173
                53e952a9-0a0a-4094-bafd-6caf33ef836d
                History

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