Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of CRF mRNA and protein in the developing ovine brain has been studied to assess the hypothesis that CRF is differentially regulated in the hypothalamus (Hypo), hippocampal-amygdala complex (H & A), frontal cerebral cortex (FCC) and brainstem (BS). We used a quantitative RNase protection assay and radioimmunoassay to determine mRNA and peptide concentrations, respectively, from the last third of gestation until term (i.e., from 95 to 142 days gestation (dg); term approximately 145 days). The major findings from this study are: (1) Hypothalamic CRF mRNA was increased by 2-fold in 140-142 dg fetuses compared to 128-138 and 95-123 dg fetuses; P = 0.016. (2) In the hypothalamus of 140-142 dg fetuses, there was a 2.5-fold increase in CRF mRNA derived from polyadenylation at poly(A) sites 2, 3 or 4; P = 0.005. (3) In 128-138 dg fetuses, CRF mRNA in the frontal cortex was 2-fold higher than in the other brain regions during this time period; P = 0.008. (4) CRF peptide concentrations in the Hypo were 2.5-fold higher in 140-142 dg fetuses compared to 95-106 and 128-138 dg fetuses; P = 0.007. (5) CRF peptide concentrations in the frontal cortex were 5.5-fold higher in 140-142 dg fetuses compared to fetuses at 95-106 dg; P = 0.004. (6) CRF peptide concentrations in the H & A were 5-fold higher in 140-142 dg fetuses compared to 95-106 dg fetuses; P = 0.029. The results from the present study demonstrate for the first time that CRF mRNA and peptide are differentially regulated in a region-specific manner during development.
Brain Res Mol Brain Res 1994 Nov
PMID:Corticotropin releasing factor mRNA and peptide levels are differentially regulated in the developing ovine brain. 787 40

To better characterize the activation products of factor B which are generated under physiologic conditions Ba was purified directly from human EDTA-plasma by immunoaffinity chromatography using anti-Ba Sepharose. SDS-PAGE analysis revealed the existence of degradation products of the Ba fragment which were truncated at the carboxyterminus. A monoclonal antibody (mAb D22/3) was produced by immunizing mice with a synthetic peptide which corresponds to the Ba carboxyterminus (Glu215-Arg234). This mAb was found to react with an epitope (Ba neo-epitope), which is newly formed after the generation of Ba from its precursor protein factor B. This neoantigenic determinant is absent both in factor B and the desArg/Lys Ba derivatives. The conversion of Ba by carboxypeptidases in human serum was monitored using an assay which is based on mAb D22/3, revealing a half-life of Ba in serum of 150 min. Furthermore, this assay allowed to quantitate plasma levels of intact and degraded Ba in healthy probands and in patients with chronic renal failure. The processing of the Ba carboxyterminus may be of functional relevance as the biological activity of the Ba fragment which had been shown to suppress human B lymphocyte functions in vitro resides in its carboxyterminal amino acid sequence.
Mol Immunol 1994 Mar
PMID:Characterization of physiologic breakdown products of the complement fragment Ba. 813 84

Studies examining the regulation of hypothalamic CRF biosynthesis have provided substantial information regarding the relevance of this peptide in neuroendocrine homeostasis. However, the consequences of elevated CRF levels within the mammalian central nervous system on regulation of CRF production within the paraventricular nucleus (PVN) of the hypothalamus remain unclear. The expression of the immediate early gene c-fos has been used and validated as a marker for neural systems activated by a variety of extracellular stimuli and has been especially useful when examining activation of central neuroendocrine systems such as those involved in the response to stressful stimuli. The present study investigates the effects of injecting CRF into the lateral ventricle of conscious rats, firstly on the expression of two separate immediate early genes, c-fos and NGFI-B within the hypothalamic PVN, and secondly on the expression of CRF mRNA itself, as determined by quantitative in situ hybridization. Expression of Fos protein was also examined by immunohistochemical techniques. Intracerebroventricular (icv) injection of CRF increased the gene expression of both c-fos and NGFI-B in the parvocellular division of the PVN 30 min after injection. Fos immunoreactivity increased in this same region between 30-60 min, whereas expression of the CRF gene itself increased 2-fold 60 min after injection and remained elevated 2 h after treatment. A positive hybridization signal for CRF was observed over Fos-immunoreactive neurons within the parvocellular division of the PVN. Finally, we observed that all CRF-induced changes in gene expression were abolished by pretreatment with the competitive CRF antagonist alpha-helical CRF-(9-41). The time-related changes in expression of the genes measured imply that the expression of both c-fos and NGFI-B occurs before a significant increase in the expression of CRF. The results also suggest that CRF may act in a positive manner to regulate its own biosynthesis.
Mol Endocrinol 1993 Oct
PMID:Corticotropin-releasing factor activates c-fos, NGFI-B, and corticotropin-releasing factor gene expression within the paraventricular nucleus of the rat hypothalamus. 826 65

cAMP participates in the regulation of endogenous hypothalamic and placental CRF by increasing levels of both peptide secretion and mRNA expression. In previous studies we have shown that stimulation of the protein kinase A-dependent pathway by cAMP analogues or forskolin produced a dose-dependent increase in levels of CRF mRNA when the intact hCRF gene was stably transfected and expressed in the mouse corticotroph AtT20 cell line. In the present study, we explored the mechanism of the cAMP-dependent increase in CRF gene expression in the stably transfected AtT20 cell line using pharmacologic, slot-blot, and RNase mapping methodologies. Following incubation with cAMP, there was a rapid increase in CRF mRNA which was completely blocked by pre-treatment with actinomycin D, an inhibitor of transcription. Cycloheximide, an inhibitor of protein synthesis, produced an independent increase in CRF mRNA, but did not change the relative induction of CRF mRNA produced by cAMP. Solution hybridization studies using intron- and exon-specific hCRF probes demonstrated a rapid rise in nuclear CRF hnRNA, which was apparent within 15 min of cAMP incubation and preceded the rise in cytoplasmic CRF mRNA. RNase mapping studies demonstrated that CRF transcription was initiated at discrete promoter sites in CRF-AtT20 cells, and that this pattern of promoter utilization was similar to that observed in mRNA derived from sites of endogenous CRF expression, human placenta and human hepatoma NPLC cell line. Treatment with cAMP selectively increased CRF mRNA transcripts initiated at the proximal promoter site, but had little or no effect on transcripts initiated at the distal promoters. We conclude that cAMP effects on CRF gene expression occur rapidly, do not require new protein synthesis, and are initiated within the nuclear compartment, consistent with a direct effect on CRF gene transcription. This effect is mediated predominantly through the proximal promoter element, while more distal promoters are less sensitive to transcriptional activation by cAMP.
Mol Cell Endocrinol 1993 Oct
PMID:Transcriptional regulation of human corticotropin releasing factor gene expression by cyclic adenosine 3',5'-monophosphate: differential effects at proximal and distal promoter elements. 827 45

High-performance liquid chromatography (HPLC) was used for the quantitation of the free amino acids in plasma and muscle samples from 34 patients with chronic renal failure; of these patients, 18 were treated by hemodialysis (HD) and 16 by continuous ambulatory peritoneal dialysis (CAPD). Depletion of taurine was observed in plasma and muscle of uremic patients, whereas methionine was normal. Cysteine sulphinic acid was present in plasma of all uremic patients. The results suggest that taurine depletion is due to decreased endogenous synthesis in uremic patients.
Biochem Mol Biol Int 1993 Feb
PMID:Application of high performance liquid chromatography in study of sulphur amino acid metabolism in uremic patients. 849 18

Expression of the POMC gene and secretion of its peptide products are under complex regulation in the pituitary by multiple factors. CRF stimulates POMC transcription and secretion in both adult anterior (AL) and intermediate (IL) pituitary lobes, whereas glucocorticoids have an inhibitory effect on POMC in the AL, but little, if any, effect in the IL. To determine when transcriptional responses elicited by these factors begin during development and whether they undergo changes during ontogeny, we used a solution hybridization/nuclease protection assay with a POMC exon 1-intron A splice junction probe to analyze simultaneously the levels of intron A-containing POMC heterogeneous nuclear RNA (hnRNA) and POMC mRNA in explant fetal and neonatal rat pituitaries. We examined responses to 8-bromo-cAMP, CRF, and dexamethasone (dex) at stages before and after innervation of the IL by dopaminergic neurons from the hypothalamus. Treatment of embryonic day 15 (e15) whole pituitaries with CRF (10(-7) M) for 1 h led to a 2.5-fold increase in the level of POMC hnRNA, while pretreatment with dex (10(-6) M) inhibited the CRF-induced stimulation of POMC transcription. These results demonstrate that by e15, POMC transcription is already responsive to both CRF and dex, and thus, functional receptors (coupled effectively to the POMC promoter) are present by this age. Initial studies of POMC mRNA levels at early postnatal ages showed that 1 mM 8-bromo-cAMP stimulated postnatal day 1 (p1) and p10 AL and neurointermediate lobe (NIL) POMC mRNA levels, and 10(-6) M dex inhibited this stimulation in p1 AL, p10 AL, and p1 NIL, but not in p10 NIL. These studies were extended to examine POMC hnRNA responses at these ages. Treatment with CRF for 1 h increased POMC hnRNA 1.9- and 1.5-fold in p1 and p10 AL, respectively, and pretreatment with dex blocked these CRF-mediated effects on AL POMC transcription. In the NIL on p1, CRF induced a 2-fold increase in POMC hnRNA, which (like that in the AL) was inhibited by 30-min pretreatment with dex; in contrast, on p10, dex did not affect the CRF-induced increase in POMC hnRNA. The glucocorticoid receptor subtype responsible for this effect was identified using treatments with specific agonist and antagonists. The type II receptor agonist RU 28362 had an effect similar to that of dex; at both 10(-6) and 10(-8) M, RU 28362 inhibited CRF-induced increases in POMC hnRNA in p1 NIL and p1 and p10 AL.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Endocrinol 1993 Apr
PMID:Developmental regulation of proopiomelanocortin gene expression in the fetal and neonatal rat pituitary. 850 39

We investigated the role of CRF in regulating receptor expression in the paraventricular nucleus (PVN). First, to clarify the effect of exogenously administered CRF, 1 microgram of ovine CRF was injected into rat lateral ventricle and changes in concentration of the CRF type 1 receptor (CRF1-R) and CRF mRNA in the PVN were semiquantified after in situ hybridization. Second, we determined the effect of stress, as a stimulant of endogenous CRF secretion, on mRNA accumulation. While CRF1-R mRNA expression was low to be undetectable in the PVN of controls, both intracerebroventricular administration of CRF and restraint significantly increased CRF1-R and CRF signals in the parvocellular PVN. Thus CRF may modulate CRF production and release from the PVN, by regulating CRF1-R expression.
Brain Res Mol Brain Res 1996 May
PMID:Corticotropin-releasing factor up-regulates its own receptor mRNA in the paraventricular nucleus of the hypothalamus. 873 81

Juvenile nephronophthisis (NPH) is a genetically heterogeneous disorder representing the most frequent inherited cause of chronic renal failure in children. We recently assigned a gene (NPH1) to the 2q13 region which is responsible for approximately 85% of cases. Cloning this region in a yeast artificial chromosome contig revealed the presence of low copy repeats. Large-scale rearrangements were detected in 80% of the patients belonging to inbred or multiplex NPH1 families and in 65% of the sporadic cases. Surprisingly, these rearrangements seem to be, in most cases, large homozygous deletions of approximately 250 kb involving an 100 kb inverted duplication. This suggests a common genetic disease-causing mechanism, which could be responsible for the highest frequency of large rearrangements reported in an autosomal recessive trait. Our findings are also of major clinical interest, as they permit the diagnosis in the majority of sporadic cases without the need for kidney biopsy.
Hum Mol Genet 1996 Mar
PMID:Large homozygous deletions of the 2q13 region are a major cause of juvenile nephronophthisis. 885 62

Significantly higher levels of plasma urea creatinine and potassium were observed in patients with renal failure compared to normal controls. The RBC sodium concentration was raised whereas the RBC potassium concentration was decreased in chronic renal failure. These alterations in the RBC Na+ and K+ concentrations were associated with decrease in ouabain sensitive sodium efflux rate and ouabain sensitive sodium efflux rate constant. However, there was no significant impact of acute hemodialysis on the intracellular electrolytes levels, ouabain sensitive sodium efflux rate and ouabain sensitive sodium efflux rate constant. These findings suggest an intrinsic alteration in the transport capacity of Na(+)-K+ pump which could account for the rise in intracellular sodium and fall in intracellular potassium content in the RBCs of chronic renal failure patients.
Biochem Mol Biol Int 1996 Dec
PMID:Modulation of ouabain sensitive sodium potassium pump of erythrocytes from patients with chronic renal failure: role of acute hemodialysis. 898 20

The present study was designed to examine the role of the nurr1/nur77 subfamily of nuclear receptor transcription factors in the regulation of the hypothalamic/pituitary/adrenal axis at the neuroendocrine level. We demonstrate that this nuclear receptor subfamily can regulate the expression of the CRF and POMC genes by interacting with a specific cis-acting sequence in their proximal promoter regions. To examine the physiological significance of this response, we have focused on the POMC gene. We provide evidence that nurr1 and nur77 are rapidly induced by CRF in primary pituitary cells and that this induction is mimicked by forskolin in an anterior pituitary cell line. Further, we demonstrate that both nurr1- and forskolin-dependent induction of a POMC-chloramphenicol acetyltransferase reporter gene are inhibited by mutation of the nurr1-binding site within the POMC promoter and that this site alone can confer cAMP responsiveness to a heterologous promoter. Finally, we provide evidence that the nurr1/nur77 response sequence is pivotal to both nurr1/nur77-dependent positive regulation and glucocorticoid receptor-dependent negative regulation of the POMC gene. These data strongly support the conclusion that the nurr1/nur77 subfamily plays an important coordinate neuroendocrine-regulatory role at all levels of the hypothalamic/pituitary/adrenal axis.
Mol Endocrinol 1997 Jan
PMID:Neuroendocrine regulation of the hypothalamic pituitary adrenal axis by the nurr1/nur77 subfamily of nuclear receptors. 899 86


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