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

Previous studies have shown that POMC mRNA and peptide levels are increased in the medial basal hypothalamus (MBH) of the chronically castrated rat and are suppressed with sex steroid replacement. In a parallel time course, hypothalamic dopamine turnover similarly changes after chronic castration and sex steroid replacement. In this study we have examined the effects of dopamine on POMC in the MBH and questioned whether the increase in dopamine activity which occurs in the MBH of chronically castrated rats is responsible for the stimulation of POMC seen under these conditions. We have therefore measured POMC gene expression and peptide content in the MBH of chronically castrated male and female rats in response to the dopamine antagonist haloperidol, and in intact or sex steroid replaced animals in response to the dopamine agonist pergolide. Adult male and female rats were studied 3-4 weeks after castration with and without testosterone (T) or estradiol (E2) replacement. POMC mRNA was measured by a solution hybridization S1 nuclease protection assay; beta-endorphin (beta-EP) and alpha-MSH were measured by RIA. In the first study 4 groups of ovariectomized (OVX) rats were treated with saline, haloperidol, E2 or E2 + pergolide. The mean POMC mRNA concentration in the MBH was 0.85 +/- 0.04 pg/microgram RNA in the saline group and decreased to 0.62 +/- 0.06 pg/microgram with haloperidol (p < 0.01). A similar decrease to 0.53 +/- 0.03 pg/microgram was seen with E2 (p < 0.01); pergolide however prevented the E2 induced decrease in POMC mRNA. In the second study ORCX rats received saline or haloperidol and sham-ORCX rats received saline or pergolide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dopamine and sex steroid regulation of POMC gene expression in the hypothalamus. 811 18

Although glucocorticoids clearly inhibit proopiomelanocortin (POMC) gene transcription and peptide synthesis in the anterior pituitary, the effects of glucocorticoids on POMC in the hypothalamus are still unclear, even though most POMC neurons in the arcuate nucleus are known to have glucocorticoid receptors. In this study, we have therefore examined the effect of adrenalectomy (ADX) and glucocorticoid replacement on POMC mRNA and peptide (beta-EP and alpha-MSH) levels in the medial basal hypothalamus (MBH) of the rat. POMC mRNA was measured by a sensitive solution hybridization S1 nuclease protection assay, and beta-EP and alpha-MSH were measured by radioimmunoassay. In a first experiment, animals were studied 7 days after ADX or sham surgery. The mean POMC mRNA concentration was 1.01+/-0.14 pg/microg RNA (means+/-SE) in the intact animals and decreased to 0.55+/-0.07 pg/microg RNA in the MBH of the ADX animals (p < 0.005). Beta-EP levels decreased in parallel from 4.30+/-0.18 to 3.36+/-0.11 ng/mg protein (p < 0.001); alpha-MSH levels decreased from 3.25+/-0.21 to 2.41+/-0.16 ng/mg protein (p < 0.005). In a second experiment, animals were studied 2 weeks after ADX. POMC mRNA levels again fell significantly from 1.15+/-0.19 pg/microg RNA in the intact animals to 0.51+/-0.06 pg/microg in the ADX animals (p < 0.01). Beta-EP levels fell also, but this was not significant. In a third experiment, all animals underwent ADX, and half of them received daily subcutaneous injections of dexamethasone (20 microg). Nine days after ADX, the mean POMC mRNA level was 0.66+/-0.04 pg/microg RNA in the saline-treated animals and increased to 0.98+/-0.08 pg/microg RNA in the dexamethasone-treated animals (p < 0.005). A parallel increase in beta-EP levels from 5.03+/-0.41 to 6.01+/-0.53 ng/mg protein was also noted, but this was not statistically significant. We conclude that POMC gene expression is significantly inhibited in the MBH at 1 and 2 weeks after ADX. This effect was reversed by glucocorticoid replacement with doses close to the physiological range. The parallel changes in POMC mRNA and peptide levels strongly suggest that, in contrast to the anterior pituitary, low doses of glucocorticoids stimulate the biosynthesis of POMC in the MBH of ADX rats.
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PMID:Glucocorticoid regulation of hypothalamic proopiomelanocortin. 948 69