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)

The proopiomelanocortin (POMC) gene is expressed in many normal nonpituitary tissues, in addition to the pituitary. POMC-derived peptides have also been detected in many pheochromocytomas. We examined poly(A)+ RNA from 5 pheochromocytomas with a POMC exon 3 riboprobe and show that 3 tumors contained POMC-like mRNAs that were 50 to 350 bases longer than pituitary POMC mRNA. S1 nuclease analyses of tumor poly(A)+ RNA demonstrate that some of the POMC-like mRNAs contain additional segments of 238, 318 or 374 nucleotides derived from the region immediately upstream from the normal transcription initiation site. We conclude that pheochromocytomas express the POMC gene and that the long POMC-like mRNAs in these tumors and, probably, those in normal adrenal and testis arise from transcription initiating at sites upstream from the normal site used in pituitary.
 ...
PMID:Proopiomelanocortin gene expression in a pheochromocytoma using upstream transcription initiation sites. 284 81

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.
 ...
PMID:Glucocorticoid regulation of hypothalamic proopiomelanocortin. 948 69