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 effects of a single intraperitoneal injection of ethanol (3 g/kg b.wt.) on the hypothalamic-pituitary-thyroid system was explored as a possible explanation of the hypothermic effect of ethanol. Serum thyroid hormones were significantly reduced by ethanol injection, but ethanol did not affect the cold-induced increase in serum thyroid hormones or thyroid-stimulating hormone (TSH). Since cold-exposure stimulates serum levels of TSH and thyroid hormones by stimulating thyroid-releasing hormone (TRH) release from neurons of the PVN, these findings demonstrate that ethanol did not block pituitary response to TRH or thyroid response to TSH. Paradoxically, ethanol increased cellular levels of TRH mRNA in the paraventricular nucleus (PVN), and blocked the cold-induced increase in TRH mRNA, suggesting that ethanol uncouples the regulation of TRH gene expression from the regulation of TRH release specifically in neurons of the PVN. Measurements of the effects of ethanol on TRH mRNA in thalamus, and beta-actin, vasopressin, somatostatin and corticotropin-releasing hormone (CRH) mRNAs in the PVN in addition to TRH mRNA revealed very specific effects of ethanol on the TRH neuronal system.
Brain Res Mol Brain Res 1992 May
PMID:Ethanol blocks the cold-induced increase in thyrotropin-releasing hormone mRNA in paraventricular nuclei but not the cold-induced increase in thyrotropin. 135 12

POMC is the precursor for a number of biologically active peptides such as ACTH, alpha-MSH, beta-MSH, and beta-endorphin. It is well known that some of these peptides, especially beta-endorphin, are involved in the regulation of reproductive functions in mammals. In order to investigate the possible role of POMC-derived peptides in the control of fish reproduction, we have cloned and sequenced two different trout POMC cDNAs called POMC A and POMC B. These cDNAs exhibited limited sequence homology (44%). The deduced amino acid sequences also showed weak similarity (43%), despite the high conservation of some peptide sequences (alpha-MSH, beta-MSH, and beta-endorphin). The POMC A coding sequence exhibited an unusual length, generating the longest endorphin ever sequenced. The long carboxy-terminal part of the beta-endorphin A contained three potential dibasic cleavage sites, allowing the occurrence of three new peptides: EQWGREEGEE, ALGE, and YHFQG. Using in situ hybridization, we found that the two POMC genes were expressed in the same pituitary cells. POMC A mRNA was the only one detectable in the hypothalamus of sexually inactive fish, whereas the two POMC genes were expressed in the hypothalamus of sexually active fish. These results indicate that two functional POMC genes are present in the rainbow trout. In POMC neurons, the expression of the POMC B gene is likely to be under the control of sexual steroids.
Mol Endocrinol 1992 Oct
PMID:One of the two trout proopiomelanocortin messenger RNAs potentially encodes new peptides. 144 14

We have created transgenic mouse lines with impaired glucocorticoid receptor function by expression of a type II glucocorticoid receptor antisense RNA in brain tissues. These animals have endocrinological characteristics similar to those seen in depression, including a hyperactive hypothalamic-pituitary-adrenal axis as indicated by elevated plasma corticosterone and adrenocorticotropin hormone levels. Treatment of transgenic animals with the tricyclic antidepressant desipramine increased hypothalamic glucocorticoid receptor mRNA concentration and dexamethasone-binding activity while decreasing plasma adrenocorticotropin hormone concentration and corticosterone levels. These results support the hypothesis that antidepressants exert action on the hypothalamic-pituitary-adrenal axis through modulation of glucocorticoid receptor gene expression.
Mol Pharmacol 1992 Dec
PMID:Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression. 148 Jan 37

The regulation of human corticotropin-releasing hormone (hCRH) gene promoter activity by inducers of cAMP was investigated by transient transfection with a construct containing the hCRH gene promoter fused to the chloramphenicol acetyltransferase gene. Expression of hCRH-chloramphenicol acetyltransferase was strongly enhanced by forskolin in the neuroblastoma SK-N-MC and choriocarcinoma JAR cell lines. Overexpression of the catalytic subunit of protein kinase A dispensed the need for forskolin, and cotransfection of cAMP-responsive element-binding protein cDNAs enhanced forskolin-dependent expression of the hCRH promoter. Progressive 5'-end deletions of the hCRH promoter delineated a cAMP- responsive region between -226 and -164 base pairs. This fragment contained the sequence TGACGTCA at -221 base pairs, consistent with the consensus motif for a CRE. A homologous oligonucleotide responded to cAMP when cloned in either orientation in front of the thymidine kinase promoter. However, the level of constitutive and inductive cAMP expression was dependent on the cell line and on intrinsic properties of the promoter. Mutation of the wild type CRH-CRE sequence into an AP-1 site (TGAGTCA) completely abolished stimulation by cAMP. In contrast, coexpression of the catalytic subunit of protein kinase A dispensed the need for stimulation with forskolin, which showed that the CRH-CRE oligonucleotide served as a functional equivalent of the native CRE element.
Mol Endocrinol 1992 Nov
PMID:Identification and characterization of a 3',5'-cyclic adenosine monophosphate-responsive element in the human corticotropin-releasing hormone gene promoter. 148 Jan 79

1. Pharmacological evidence indicates that stress induced by brief (14 to 20-day) social deprivation in the rat is associated with an activation of the central preproenkephalin (ENK) opioid system. This study examines the neurochemical evidence that substantiates such an activation. 2. Using a specific ENK complementary DNA probe, ENK RNA levels were measured by dot blot and Northern blot analyses in different brain areas of socially deprived rats. Immunoreactivity to met-enkephalin-derived peptides was also evaluated by radioimmunoassay in the same brain regions. 3. Brief social deprivation increased the levels of ENK RNA and enkephalin immunoreactivity in whole hypothalamus. 4. Our data suggest that this type of stress appears to be associated to an induction of ENK gene transcription in hypothalamus.
Cell Mol Neurobiol 1992 Dec
PMID:Preproenkephalin RNA increases in the hypothalamus of rats stressed by social deprivation. 149 Feb 74

Dog hearts divided into right and left atria, right and left ventricles and intraventricular septum were homogenized in acid for extraction. Total opioids, and specific peptides (methionine-enkephalin, methionine-enkephalin-arg6-gly7-leu8) were determined by radioreceptor and radioimmunoassay, respectively. Catecholamines were quantitated amperometrically following HPLC. The effects of anesthetic agents (pentobarbital, alpha-chloralose), hemorrhage and ganglionic blockade (hexamethonium and atropine) were evaluated. Total opioids, enkephalins and epinephrine were distributed uniformly throughout the myocardium, while norepinephrine was preferentially concentrated in the atria. Immunoreactive methionine-enkephalin accounted for only 1 to 2% of the total cardiac opioids estimated by radioreceptor assay. Hemorrhage lowered methionine-enkephalin content throughout the myocardium with no significant effect on total opioids or catecholamines. Ganglionic blockade increased total opioid, methionine-enkephalin-arg6-gly7-leu8 and catecholamine content without altering methionine-enkephalin content. HPLC of left ventricular extracts demonstrated that 50% of met-enkephalin-immunoreactivity eluted at retention times equal to synthetic metenkephalin. In summary, there appears to be substantive opioid concentrations within canine myocardium which respond to physiological and pharmacological interventions. These cardiac opioid responses do not parallel changes observed for catecholamines under the same conditions.
J Mol Cell Cardiol 1992 Jan
PMID:Screening for opioids in dog heart. 156 31

In the intermediate lobe of the pituitary gland, the prohormone proopiomelanocortin (POMC) is processed to, among other peptides, melanocyte-stimulating hormone (alpha-MSH). In the toad Xenopus laevis alpha-MSH controls skin darkening during background adaptation, and the level of POMC gene transcription in the intermediate lobe depends on the color of the background. In the lobe, two structurally different POMC proteins are produced from two mRNAs that are transcribed to approximately the same level from two POMC genes (A and B). We previously reported the entire nucleotide sequence of Xenopus POMC gene B. To identify conserved-- and thus potential regulatory--DNA elements in the Xenopus POMC gene, we here report the determination and analysis of the complete nucleotide sequence of Xenopus POMC gene A and its 5'- and 3'-flanking regions. Comparison of the two Xenopus POMC genes revealed, in addition to the exons, three highly conserved regions. First, the promoter regions are greater than 90% identical. The second region concerns JH12 repetitive elements situated at approximately the same position in both genes. These elements are greater than 86% identical. The third region is a 500-bp sequence just upstream of exon three (63% identity). Besides these three large regions, several small regions with significant identity were found at similar positions in the two POMC genes. The fact that, except for the JH12 element, the repetitive elements are not conserved between the two POMC genes indicates that these repeats are not functionally important.
Mol Biol Evol 1992 May
PMID:Comparative structural analysis of the transcriptionally active proopiomelanocortin genes A and B of Xenopus laevis. 158 15

Secretion of beta-endorphin from mouse pituitary AtT20 cells is stimulated by a variety of compounds that raise intracellular cAMP and Ca2+. To investigate the role of cAMP-dependent protein kinases in secretion, AtT20 cells were transfected with an expression vector coding for a regulatory (R) subunit of cAMP-dependent protein kinase containing mutations in both cAMP-binding sites. Expression of the mutant regulatory subunit in stable transformants (RAB cells) results in a dominant inhibition of cAMP-dependent protein kinase activity. Isoproterenol (1 microM) or analogs of cAMP stimulated beta-endorphin secretion from AtT20 cells, but failed to stimulate secretion in RAB cells expressing the mutant R subunit. Secretion in response to CRF (100 nM) was inhibited by 80% in these mutant clones, whereas the secretory response to vasoactive intestinal peptide (VIP; 100 nM) or phorbol ester (100 nM phorbol myristate acetate) was not inhibited by the R subunit mutation. Intracellular cAMP was elevated in response to CRF (11- to 15-fold), isoproterenol (5- to 10-fold), and VIP (4- to 8-fold) in RAB cells. Similar concentrations of VIP were required to evoke beta-endorphin secretion in either RAB cells or AtT20 cells. As with most secretagogues, VIP-induced secretion was inhibited in the presence of either EGTA or a voltage-sensitive Ca2+ channel antagonist, PN200-110. The secretory response to VIP was unaffected by down-regulation of protein kinase-C. These results suggest that CRF and isoproterenol work via cAMP-dependent protein kinase to activate beta-endorphin secretion, whereas VIP can act by a different mechanism that does not involve cAMP-dependent protein kinase or protein kinase-C.
Mol Endocrinol 1991 Feb
PMID:Role of cyclic adenosine 3',5'-monophosphate-dependent protein kinase in hormone-stimulated beta-endorphin secretion in AtT20 cells. 164 51

Peptides derived from prodynorphin and preproenkephalin are located in GABAergic striatal projection neurons. We have used nucleic acid hybridization techniques to investigate the role of GABA in the regulation of striatal opioid peptide gene expression. Rats were treated with the GABA-transaminase inhibitors aminooxy acetic acid, ethanolamine O-sulphate and gamma-vinyl-GABA for one week. The GABA levels in the striatum were significantly elevated after each treatment. The GABA-transaminase-inhibitors decreased the striatal levels of the opioid peptides met-enkephalin and dynorphin(1-8) and concomitantly decreased the concentrations of the mRNAs coding for proenkephalin and prodynorphin. These findings indicate that GABA exerts an inhibitory influence on prodynorphin and proenkephalin gene expression in the striatum. The mechanisms underlying these inhibitions are discussed.
Brain Res Mol Brain Res 1991 Apr
PMID:GABAergic regulation of striatal opioid gene expression. 164 82

The effects of opioid peptides on a 1.1-kb long proopiomelanocortin messenger RNA (POMC mRNA) have been investigated in rat hypothalamic cells maintained in culture. Most opioid peptides exerted an inhibitory control on POMC mRNA steady-state concentrations. beta-Endorphin caused a 65% maximal inhibitory effect (IC50 = 6.1 x 10(-9) M) while slightly less inhibition was caused by Met- and Leu-enkephalin, dynorphin A and DADLE ([D-Ala2,D-Leu5] enkephalin). The effects of beta-endorphin and of Met-enkephalin were completely reversed by the delta opioid antagonist ICI 174,864 while the kappa-receptor specific antagonist binaltorphimine or the sigma-receptor specific antagonist DTG (1,3-di(2-tolyl) guanidine) respectively blocked the inhibitory actions of dynorphin A and of DADLE. The mu-receptor specific agonist DAGO ([D-Ala2,N-Me-Phe4,Gly5-OL]enkephalin) did not affect POMC mRNA levels. The failure of the dopaminergic D2 antagonist haloperidol to modify the inhibitory effects of opioid peptides argues for a direct inhibitory opioid peptide modulation of hypothalamic POMC mRNA levels mediated by the delta-, kappa- and sigma- (but not mu-) receptors in vivo.
Brain Res Mol Brain Res 1991 May
PMID:Regulation of proopiomelanocortin messenger RNA concentrations by opioid peptides in primary cell cultures of rat hypothalamus. 164 65


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