Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anterior pituitary POMC transcription and peptide release are negatively regulated by glucocorticoids and stimulated by CRF. Although pretreatment of corticotrope cells with CRF markedly inhibits subsequent glucocorticoid effects, the mechanism of this action is unclear. We have thus used a mouse corticotrope tumor (AtT20) cell line, to examine the effects of CRF on glucocorticoid receptor (GR) messenger RNA levels and on GR capacity/nuclear translocation. GR mRNA levels were measured by solution hybridization/S1 nuclease protection, and both total cell binding and nuclear binding were determined with [3H]dexamethasone ([3H]DEX). CRF treatment of AtT20 cells led to a rapid time-dependent decrease in GR mRNA levels which preceded a dose- and time-dependent decrease in GR binding capacity. Scatchard analysis showed a single class of high affinity binding sites (GR) in both control and CRF-treated cultures, and a decrease in the total number of GR after CRF treatment. The relative proportion of nuclear vs. cytoplasmic localized [3H]DEX-bound GR did not differ between control and CRF-treated cultures, indicating that CRF does not interfere with GR nuclear translocation. To investigate whether CRF regulates GR expression through the adenylate cyclase system, as it does POMC, AtT20 cells were treated with either forskolin or 8-bromo-cAMP, and specific nuclear GR binding was determined. Both drugs mimic the CRF-induced decrease in GR binding, and in addition forskolin decreased GR mRNA levels; in contrast, forskolin had no effect on GH3 cell GR levels. These results suggest that CRF can decrease the cellular concentration of GR, and thus potentially the response to glucocorticoids, through the same mechanism by which it stimulates anterior pituitary POMC expression.
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PMID:Adrenocorticotropin-releasing factor down-regulates glucocorticoid receptor expression in mouse corticotrope tumor cells via an adenylate cyclase-dependent mechanism. 185 64

The present study was designed to characterize the regulation of the type II corticosteroid receptor (GR) mRNA in two tissues involved in the control of the hypothalamic-pituitary-adrenal axis. We have used a solution hybridization/S1 nuclease protection assay to quantitate GR mRNA levels in the rat hippocampus and anterior pituitary after CRF, dexamethasone (DEX), or corticosterone (CORT) treatment. In general, hippocampal GR mRNA levels increased after removal of endogenous corticosteroids by surgical adrenalectomy and decreased in response to glucocorticoid treatment. More specifically, in the hippocampus 1) GR mRNA expression was decreased when adrenalectomized (ADX) animals were replaced with a relatively low dose of CORT, but not with a low dose of DEX; 2) acutely, CRF was more effective than DEX in decreasing the levels of GR mRNA in intact animals; however, under the same paradigm in ADX animals, DEX decreased the level of GR mRNA, whereas CRF was ineffective; and 3) in contrast to the decrease in GR mRNA levels observed after acute and low doses of glucocorticoid treatment, chronic treatment with either DEX or CORT did not change the level of hippocampal GR mRNA. These results suggest that in the hippocampus the decrease in GR mRNA expression after CRF treatment is probably via the release of glucocorticoids, and that this tissue is more sensitive to endogenous glucocorticoids than DEX. Anterior pituitary GR mRNA was differentially regulated compared with that in the hippocampus. In marked contrast to Gr mRNA in the hippocampus, ADX did not alter anterior pituitary GR mRNA expression, and glucocorticoid treatment led to an increase in GR mRNA levels. In the anterior pituitary 1) glucocorticoid treatment led to an increase in GR mRNA expression, when replaced with a relatively low dose of DEX, but not when replaced with a low dose of CORT; 2) acutely, neither CRF nor DEX altered levels of GR mRNA in intact animals; however, under the same paradigm DEX increased levels in ADX animals; and 3) chronic DEX or CORT treatment of intact animals elevated levels of anterior pituitary GR mRNA. In summary, these data have demonstrated tissue-specific regulation of GR mRNA in the hippocampus and anterior pituitary, which is dependent on both the dose and length of treatment and, in addition, on the glucocorticoid itself.
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PMID:Differential regulation of type II corticosteroid receptor messenger ribonucleic acid expression in the rat anterior pituitary and hippocampus. 236 79