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)

Reverse-phase high-performance liquid chromatography analysis, coupled with a sensitive radioimmunoassay for alpha-melanocyte-stimulating hormone (alpha-MSH), was used to characterize the alpha-MSH-related peptides stored in the rat hypothalamus or released from perifused hypothalamic slices. Four peaks of alpha-MSH-like immunoreactivity (alpha-MSH-LI) co-eluting with synthetic des-N alpha-acetyl alpha-MSH, alpha-MSH and their respective sulfoxide derivatives were resolved and quantified. In hypothalamic extract, deacetyl alpha-MSH which was the predominant peptide represented 94.4% of total alpha-MSH-LI content, while the relative amount of alpha-MSH was only 5.6%. Analysis of alpha-MSH-related peptides contained in effluent perifusates showed that deacetyl alpha-MSH and its oxidized form were the major peptides released from neurons in basal conditions or under KCl-induced depolarization (50 mM KCl for 75 min). However, the proportion of acetylated peptide was 3-4 times higher in the perifusion medium than in hypothalamic extracts. Our data indicate that acetylation of des-N alpha-acetyl alpha-MSH may occur during the process of exocytosis. Since acetylation of alpha-MSH markedly increases the behavioural potency of the peptide, these results suggest that regulation of the acetyltransferase activity could be a key mechanism to modulate the bioactivity of alpha-MSH-related peptides in the brain.
Brain Res Mol Brain Res 1989 May
PMID:Characterization of alpha-MSH-related peptides released from rat hypothalamic neurons in vitro. 254 17

Mouse melanoma cells in culture respond to melanocyte-stimulating hormone (MSH) by demonstrating increased activity of tyrosinase, the rate-limiting enzyme for melanin synthesis. Because this stimulation is strictly dependent upon continued transcription and translation, we have carried out studies to determine if MSH increases the level of tyrosinase mRNA. The abundance of tyrosinase message levels in melanoma cells treated with either MSH or dibutyryl cAMP was determined by Northern blot analysis utilizing a 946 base pair mouse tyrosinase cDNA probe. The tyrosinase cDNA was isolated from a lambda gt11 expression library generated from mRNA isolated from theophylline-induced Cloudman melanoma cells. The abundance of tyrosinase mRNA was determined in an amelanotic cell clone (AM-7AS) and a melanotic cell clone (MEL-11AS). The melanotic cell line had five times as much tyrosinase activity and almost 10 times more tyrosinase mRNA than the amelanotic line. Tyrosinase activity and mRNA increased in both cell lines after MSH addition. The amelanotic line treated with MSH for three days showed a fivefold increase in tyrosinase activity and a twofold increase in tyrosinase mRNA. The melanotic cell line treated with MSH for three days showed a 3.7-fold increase in enzyme activity and an eightfold increase in the abundance of tyrosinase mRNA. Dibutyryl cAMP also stimulated tyrosinase activity and the accumulation of tyrosinase mRNA. The data suggest that MSH, acting through cAMP, promotes an accumulation of tyrosinase mRNA.
Somat Cell Mol Genet 1989 May
PMID:Regulation of tyrosinase mRNA levels in mouse melanoma cell clones by melanocyte-stimulating hormone and cyclic AMP. 254 86

Rat adrenal glomerulosa cells labelled for 18 h with [3H]inositol responded to angiotensin II with a dose-dependent stimulation of the accumulation of inositol monophosphate, inositol bisphosphate and inositol trisphosphate. Addition of adrenocorticotropic hormone (ACTH) (10(-7)M) reduced the maximum responses without altering the EC50 values for angiotensin II. Thus, ACTH acted as a non-competitive inhibitor with respect to angiotensin II. No inhibition was observed in cells labelled for 2 h with [3H]inositol. Detailed examination of the inhibition showed that ACTH(1-24) was the most potent inhibitor, with ACTH(1-39) being 10-fold less potent. A mixture of alpha-melanocyte-stimulating hormone (alpha-MSH) (ACTH(1-13] and corticotropin-like intermediate lobe peptide (ACTH(18-39] was similarly inactive. ACTH(5-24) did not produce detectable inhibition. In terms of specificity, the receptor mediating ACTH inhibition of phosphatidylinositol turnover was similar to the receptor which mediated stimulation of aldosterone synthesis. Inhibition by ACTH was additive with inhibition produced by dibutyryl cAMP demonstrating that it was not mediated by rises in intracellular cAMP. ACTH inhibition also was additive with inhibition by the calcium channel blocker, nifedipine. These results demonstrate an interaction between ACTH receptors and angiotensin II receptors in adrenal glomerulosa cells at the level of their receptor-second messenger pathways.
Mol Cell Endocrinol 1989 May
PMID:Adrenocorticotropic hormone inhibits angiotensin II-stimulated inositol phosphate accumulation in rat adrenal glomerulosa cells. 254 42

The contribution of voltage-operated calcium (VOC) channels in the mechanism of release of alpha-melanocyte-stimulating hormone (alpha-MSH) from hypothalamic neurons was investigated using perifused rat hypothalamic slices. The stimulatory effect of potassium (50 mM) on alpha-MSH release was completely blocked by cadmium (1 mM) a calcium competitor which indifferently blocks T-, L-and N-type VOC channels. To determine the nature of calcium conductances involved in K+-evoked alpha-MSH release, we have investigated the effect of a VOC channel agonist and 3 antagonists on the secretion of the neuropeptide. Administration of synthetic omega-conotoxin fraction GVIA (1 microM), a peptide toxin which blocks both N- and L-type VOC channels, reduced by 33% K+-induced alpha-MSH release. In contrast, the 1,4-dihydropyridine (DHP) antagonist nifedipine, at concentrations up to 100 microM, did not affect the response of hypothalamic alpha-MSH neurons to depolarizing concentrations of KCl. In addition, the secretion of alpha-MSH induced by high K+ concentrations was not reduced by nifedipine (10 microM) in the presence of diltiazem (1 microM), a benzothiazepine derivative which increases the affinity of the DHP antagonist for L-type VOC channels. The DHP agonist BAY K 8644 (0.1-10 microM) did not modify the early phase of the response of alpha-MSH neurons to K+-induced depolarization. In contrast BAY K 8644 (1 or 10 microM) significantly prolonged the duration of K+-induced alpha-MSH release. This sustained release of alpha-MSH induced by BAY K 8644 (10 microM) was totally suppressed by nifedipine (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1989 Jul
PMID:Involvement of voltage-operated calcium channels in alpha-melanocyte-stimulating hormone (alpha-MSH) release from perifused rat hypothalamic slices. 254 28

The effect of arginine vasopressin (AVP) and corticotropin releasing factor (CRF) an adrenocorticotropin (ACTH) secretion, phosphatidylinositol breakdown and cAMP accumulation was examined in primary cultures of mouse anterior pituitary cells. AVP and CRF added alone stimulated ACTH secretion in a dose-dependent manner. At 10(-8) M concentration of peptide, AVP and CRF stimulated ACTH secretion 2.8- and 4.6-fold, respectively. AVP and CRF added in combination at equal doses gave an additive effect. CRF enhanced cAMP accumulation, but AVP had no effect on basal or CRF-induced cAMP accumulation. Both forskolin (10(-5) M) and 8-bromo-cAMP (10(-3) M) increased ACTH secretion in these cells by 2.8- and 1.7-fold, respectively. AVP induced the breakdown of phosphoinositides, and CRF alone, or in combination with AVP did not modify this effect. Phorbol 12-myristate 13-acetate (10(-7) M), dioctanoylglycerol (10(-4) M) and phospholipase C (100 mU/ml) also stimulated ACTH secretion in these cells by 4.2-, 2.4-, and 3.7-fold, respectively. Depletion of intracellular and extracellular Ca2+ decreased ACTH secretion, but had no significant effect on CRF-induced cAMP accumulation. However, AVP-induced phosphoinositide breakdown was dependent on extracellular Ca2+. These results indicate that CRF stimulates ACTH secretion via the cAMP-dependent pathway and AVP via the phosphoinositide breakdown-phospholipase C pathway. In the presence of AVP and CRF, both pathways appear to operate independently to produce an additive effect on ACTH secretion.
Mol Cell Endocrinol 1989 Aug
PMID:Transmembrane signals mediating adrenocorticotropin release from mouse anterior pituitary cells. 255 Feb 96

Recent studies have shown that both proopiomelanocortin (POMC)-derived peptides and a range of POMC gene transcripts are present in the testis. Previous immunocytochemical studies have reported immunoreactive (ir)-beta-endorphin (EP) and ir-ACTH to be localized in the Leydig cells, and ir-NacEP in spermatogonia and primary spermatocytes. In the present study, we have further examined the hypothesis that testicular Leydig cells are the principal site of synthesis of these peptides, by determining the effects of the administration of the cytotoxic drug ethane dimethane sulphonate (EDS) which selectively destroys the Leydig cells of the testis. As expected, serum testosterone levels fell and serum FSH/LH levels increased within 3 days of EDS administration, returning to normal levels 4-8 weeks later. In contrast, the testicular content of POMC-derived peptides and POMC mRNA levels in these animals was not significantly altered throughout the experimental period. In addition, POMC mRNA was not detected in a purified Leydig cell preparation derived from adult male rats, and POMC-derived peptides were also undetectable in the media of a similar preparation following cell culture. These data suggest that in the adult the predominant site of rat POMC gene expression is in testicular interstitial cells other than Leydig cells.
Mol Cell Endocrinol 1989 Aug
PMID:Effect of ethane dimethane sulphonate on proopiomelanocortin (POMC) mRNA and POMC-derived peptides in the rat testis. 255 Feb 99

Specific DNA sequence elements which contain binding sites for the glucocorticoid receptor mediate the action of glucocorticoid hormones on gene transcription. In glucocorticoid-inducible genes, these glucocorticoid-responsive elements behave as hormone-inducible enhancers of transcription. We have taken advantage of the bovine papillomavirus (BPV) system to test the stringency of glucocorticoid regulation of transcription. BPV episomes were constructed to contain two hormone-regulated transcription units in close proximity; one transcription unit is under control of a glucocorticoid-inducible promoter (mouse mammary tumor virus) while the other is under control of a glucocorticoid-inhibited promoter (pro-opiomelanocortin). Glucocorticoids independently regulated transcription of the two physically linked transcription units, irrespective of their relative orientation and of their proximity on the BPV episomes. This result contrasts with the so-called position-independent activity of enhancers and suggests that the multicomponent organization of eucaryotic promoters restricts the action of hormone-responsive regulatory elements to a specific transcription unit, thus accounting for the stringency of hormonal regulation observed in vivo.
Mol Cell Biol 1989 Jul
PMID:Independent glucocorticoid induction and repression of two contiguous responsive genes. 255 Jul 96

The effect of immobilization stress on the expression of c-fos protein in the adrenal cortex of adult rats was investigated immunocytochemically. After immobilization stress lasting for longer than 30 min, an enhanced c-fos-like immunoreactivity was observed in the cortical cells of the zona fasciculata and zona reticulata. Compared to unstressed controls, an about 5-fold increase in the density of the immunoreactive cells in a unit of the cortical area was seen following a 1-h immobilization. The enhanced immunoreactivity lasted for at least 3 h after 1-h immobilization and it began to diminish 5 h after the stress. Furthermore, administration of dexamethasone 2 h prior to 1-h immobilization attenuated the stress-enhanced immunostaining for the c-fos-like protein. These results suggest that an acute stress may cause a dramatic and long-persisting induction of c-fos-like protein in the cortical cells of rat adrenals. The characteristic zonal distribution of the c-fos induction in rat adrenals as well as the effect of dexamethasone suggest involvement of the pituitary adrenocorticotropic hormone (ACTH) in the induction.
Mol Cell Endocrinol 1989 Oct
PMID:Induction of c-fos-like protein in the rat adrenal cortex by acute stress--immunocytochemical evidence. 255 26

Hypothalamic dopamine (DA), acting at DA D2-receptors (D2-R) on pituitary target cells, mediates peptide release and biosynthesis of rat pituitary anterior lobe (AL) prolactin, and neurointermediate lobe (NIL) pro-opiomelanocortin (POMC). We were interested in determining if dopamine agonists and antagonists were capable of modifying D2-R gene expression in these pituitary cells. Utilizing the recently published sequence of the rat D2-R, we isolated a rat D2-R cDNA clone by polymerase chain reaction, and have synthesized RNA probes to quantitate levels of D2-R mRNA by solution hybridization/nuclease protection assay. We report here that 5-day administration of the DA antagonist haloperidol led to significant increases in both D2-R mRNA and POMC mRNA in the NIL; the DA agonist bromocriptine caused a significant decrease in NIL POMC mRNA with no parallel change in D2-R mRNA. In contrast, no significant changes in D2-R mRNA in AL were observed following treatment with either the DA agonist or antagonist. These data provide evidence for tissue-specific regulation of D2-R mRNA in response to dopaminergic manipulation.
Mol Cell Endocrinol 1989 Nov
PMID:Dopamine D2-receptor messenger RNA is differentially regulated by dopaminergic agents in rat anterior and neurointermediate pituitary. 257 47

Glucocorticoids rapidly and specifically inhibit transcription of the pro-opiomelanocortin (POMC) gene in the anterior pituitary, thus offering a model for studying negative control of transcription in mammals. We have defined an element within the rat POMC gene 5'-flanking region that is required for glucocorticoid inhibition of POMC gene transcription in POMC-expressing pituitary tumor cells (AtT-20). This element contains an in vitro binding site for purified glucocorticoid receptor. Site-directed mutagenesis revealed that binding of the receptor to this site located at position base pair -63 is essential for glucocorticoid repression of transcription. Although related to the well-defined glucocorticoid response element (GRE) found in glucocorticoid-inducible genes, the DNA sequence of the POMC negative glucocorticoid response element (nGRE) differs significantly from the GRE consensus; this sequence divergence may result in different receptor-DNA interactions and may account at least in part for the opposite transcriptional properties of these elements. Hormone-dependent repression of POMC gene transcription may be due to binding of the receptor over a positive regulatory element of the promoter. Thus, repression may result from mutually exclusive binding of two DNA-binding proteins to overlapping DNA sequences.
Mol Cell Biol 1989 Dec
PMID:Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription. 258 21


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