Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complete exonic and partial intronic sequence of the bovine CYP17 (P45017 alpha) gene has been determined. The gene contains eight exons with exon/intron boundaries which are identical to those determined previously for the human CYP17 gene. The site of initiation of transcription of this gene is located within a 6-base sequence 52 bp from the initiation of translation. Considerable sequence homology (58.7%) is found when approximately 500 bp of the 5'-flanking sequences of the bovine and human CYP17 genes are compared. A computer-based search of this region of bovine CYP17 for consensus sequences associated with binding of transcription factors (i.e., GR, PR, CREB/ATF, AP1, AP2, AP3, AP4, AP5, OTF, CTF/NF1, SP1) shows only the consensus CREB/ATF sequence TGACGT which is also found to be at approximately the same position in the human CYP17 gene. In bovine adrenal cortex, transcription of the CYP17 gene is regulated by the peptide hormone adrenocorticotropin via cAMP. Whether the consensus CREB/ATF sequence is associated with the cAMP-mediated transcription of the CYP17 gene remains to be elucidated.
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PMID:Structural characterization of the bovine CYP17 (17 alpha-hydroxylase) gene. 254 97

Although corticotropin releasing factor (CRF) and glucocorticoid hormones (GC) act directly at the level on the anterior pituitary corticotrope cell to stimulate (CRF) or inhibit (GC) pro-opiomelanocortin (POMC) expression, the actions of GC on POMC have been shown to be impaired if corticotrope cells are coincubated or preincubated with CRF. In the present study we have measured secreted beta-endorphin (beta EP) and changes in the level of nuclear POMC hnRNA as an indirect measure of gene transcription to characterize the molecular mechanisms involved in the CRF-mediated inhibition of glucocorticoid action. In primary cultures of rat anterior pituitary cells either co-treated or pretreated with CRF, acute dexamethasone (DEX)-mediated inhibition of POMC hnRNA levels was impaired. In contrast, the ability of CRF to block glucocorticoid action was abolished if the cells were pretreated with the protein synthesis inhibitor puromycin. Since previous studies have demonstrated that components of the AP1 transcription factor can modulate glucocorticoid receptor activity in other systems, we examined the regulation of the proto-oncogenes c-fos and c-jun in response to CRF. Treatment of the corticotrope cell line (AtT-20) with CRF rapidly activated c-fos mRNA to levels 11-12-fold above control by 30 and 60 min, with no apparent elevation of c-jun mRNA levels. Pretreatment of AtT-20 cells with antisense c-fos oligonucleotides prevented CRF from blocking glucocorticoid inhibition of POMC hnRNA levels and beta EP release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Corticotrope responsiveness to glucocorticoids is modulated via rapid CRF-mediated induction of the proto-oncogene c-fos. 837 73

The POMC gene, encoding a hormonal precursor protein, is primarily expressed in the pituitary in a tissue-specific manner. The POMC gene is transcriptionally regulated by a variety of hormones and neuropeptides and the second messengers cAMP and Ca++. Using the corticotrope-derived AtT20 cell line, we have previously shown that overexpression of cFos stimulates POMC transcription. The aim of this work was to analyze whether cFos directly interacts with the POMC gene in basal and corticotropin-releasing hormone (CRH) stimulated cells. Using progressively deleted POMC promoter sequences or heterologous promoter constructs coupled to the chloramphenicol acetyl transferase reporter gene, we demonstrate the existence of a major cFos- responsive sequence within the first exon of the POMC gene. This sequence, TGACTAA, appears functionally indistinguishable from the canonical AP1 binding site. When fused to a minimal promoter, this sequence confers inducibility by cFos and CRH. Gel shift analyses with CRH-stimulated AtT20 nuclear extracts or in vitro synthesized proteins revealed that this sequence efficiently binds Fos and Jun. Expression of c-fos anti-sense mRNA reduced CRH-stimulated POMC transcription, thus indicating that, at least in part, cFos mediates the effect of CRH on POMC transcription. However, deletion of this major exonic AP1 site from the POMC constructs greatly reduced the effect of c-fos overexpression but did not suppress POMC stimulation by CRH, indicating that CRH stimulates POMC transcription by one or more cFos-independent mechanism(s).
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PMID:Corticotropin-releasing hormone stimulates proopiomelanocortin transcription by cFos-dependent and -independent pathways: characterization of an AP1 site in exon 1. 859 20

Expression of the adrenocorticotropin receptor (MC2-R) is restricted to adrenocortical cells and is up-regulated by both adrenocorticotropin and angiotensin II through the activation of protein kinase A and protein kinase C pathways, respectively. After cloning of the promoter region of the human MC2-R gene (hMC2-R), we have shown that cyclic AMP-induced regulation of transcriptional activity of the gene is achieved through two SF1 binding elements located in the proximal promoter. On the other hand, regulation by angiotensin II partly involved two AP1 binding sites. Using different primary cell cultures, we have also been able to delineate a region inside the promoter which is responsible for part of the tissue-specific expression of the gene.
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PMID:The human MC2-R gene expression: different aspects of its control. 1253 Jun 26

Stress induces tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) gene expression in sympathetic ganglia and adrenal medulla (AM). However, distinct molecular mechanisms appear to regulate these genes in these locations. The elevation of TH mRNA in response to single immobilization stress (IMO) in AM is robust, but transient, while the induction of TH and DBH mRNAs in sympathetic ganglia is slower and more long lasting. Injections of adrenocorticotropic hormone (ACTH) elicited induction of TH and DBH gene expression in rat sympathetic ganglia, but not in AM. The superior cervical (SCG) and stellate (StG) ganglia, but not AM, were found to express mRNA for the MC-2 receptor, the major ACTH responsive receptor in adrenal cortex. IMO led to increase in MC-2 receptor mRNA levels in SCG. Thus, ACTH, via the MC-2 receptor, may be directly involved in the stress-elicited regulation of norepinephrine biosynthesis in sympathetic ganglia. The signaling pathways triggered by IMO differed in these locations. In AM, IMO triggered activation of the MAP kinase, JNK, and induction of AP1 factors, Egr1 and phosphorylation of CREB. In contrast in the SCG, with IMO we did not observe changes in JNK and little binding to the AP1 motif of the TH promoter. However, there was an increase in CREB binding to the CRE site of the TH promoter. The results reveal differential mechanisms of regulation of catecholamine biosynthetic enzymes by stress in two components of the sympathoadrenal system and should provide basis for possible selective pharmacologic interventions.
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PMID:Molecular regulation of gene expression of catecholamine biosynthetic enzymes by stress: sympathetic ganglia versus adrenal medulla. 1524 Mar 92

Starvation is known to activate the hypothalamo-pituitary-adrenal (HPA) axis, a representative antistress system in the living organism. In this study, we investigated in vitro whether activation of the AMP-activated protein kinase (AMPK), which is known to occur in intracellular energy depletion, influences the expression of POMC gene that encodes adrenocorticotropin. We first confirmed that each subunit of AMPK was expressed in the AtT20 corticotroph cell line. We then found that AICAR, a cell-permeable AMP analog and an activator of AMPK, potently stimulated the 5'-promoter activity of POMC gene in a dose-dependent manner. The effects were promoter specific because AICAR enhanced the AP1-mediated POMC promoter activities but did not influence other transcription factor-induced transcription. The effect of AICAR on POMC gene transcription was completely eliminated by specific AMPK inhibitor compound C or by dominant negative AMPK, whereas overexpression of constitutively active AMPK mimicked the effect of AICAR. Finally, experiments using specific kinase inhibitors suggested that the PI 3-kinase-mediated signaling pathway is at least partly involved in the effect. Our results suggest that intracellular energy depletion with the resultant activation of AMPK directly stimulates the HPA axis at the pituitary level by increasing the expression of POMC gene.
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PMID:Activation of AMP-activated protein kinase stimulates proopiomelanocortin gene transcription in AtT20 corticotroph cells. 1734 51

While lipopolysaccharides (LPS) are known to activate the hypothalamo-pituitary-adrenal axis, their direct effects on proopiomelanocortin (POMC) and adrenocorticotropin (ACTH) expression at the pituitary level through Toll-like receptors (TLRs) remain unclear. In this study, we examined the effects of LPS on ACTH secretion and the transcription of the POMC gene in the AtT20 mouse pituitary corticotroph cell line. RT-PCR analysis showed that TLR1-4 and 6 subtype mRNAs were expressed in AtT20 cells. When the cells were treated with LPS, a significant increase in the 5'-promoter activity of POMC gene was observed at 24 h, without any stimulatory effect on ACTH secretion. LPS also stimulated the expression of c-Fos gene and protein, and AP1-, but not NF-kappaB-, mediated transcription. Overall, our data show the expression of TLRs in the pituitary corticotroph cells, and suggest the direct stimulatory effect of LPS on POMC gene expression via TLR (probably TLR4), although the intracellular signaling pathways in the corticotroph may be different from those in immune cells.
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PMID:Lipopolysaccharide stimulates proopiomelanocortin gene expression in AtT20 corticotroph cells. 1832 74