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)

Expression of mRNAs coding for the ACTH secretagogues corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) was examined in the hypothalamic paraventricular nucleus (PVN) of rats bearing hippocampal lesions. Either total hippocampectomy (HPX) or extirpation of the dorsal hippocampus (DHPX) precipitated a 4-fold increase in CRF mRNA expression relative to sham-operated controls (SHAM), as determined by semiquantitative in situ hybridization histochemistry. AVP mRNA was localized to individual parvocellular neurons of the medial parvocellular division of the PVN in only the HPX and DHPX groups, consistent with enhanced production of AVP message in this neuronal population subsequent to hippocampal damage. HPX did not affect AVP mRNA content in magnocellular divisions of PVN. Plasma beta-endorphin levels were significantly elevated in the HPX and DHPX groups relative to SHAM animals, indicating a chronic increase in release of proopiomelanocortin peptides from the anterior pituitary gland in response to hippocampal lesion. Circulating corticosterone levels were elevated in HPX rats as well. To control for effects of lesion size and location, additional animals received large ablations of cerebral cortex or cerebellum. In neither case was CRF or AVP mRNA significantly altered in the PVN. The results suggest that the hippocampus exercises a tonic inhibitory role on ACTH secretagogue production in neuroendocrine neurons promoting ACTH release.
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PMID:Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis. 279 52

The authors have studied mechanisms which could be involved in the sustained activation of the hypothalamus-pituitary-adrenal (HPA) axis during continuous infusion of rats with recombinant human interleukin-1beta (IL-1beta). First, the effects of 3 days of intracerebroventricular (i.c.v.) infusion of rats with IL-1 on plasma adrenocorticotropin (ACTH) and corticosterone (B) levels were investigated. Thereafter, changes in plasma ACTH and B levels were followed in rats intraperitoneally (i.p.) infused with IL-1beta after immunoneutralization of corticotropin-releasing hormone (CRH), hypophysectomy (HPX), macrophage depletion using dichloromethylene diphosphonate (Cl2MDP)-containing liposomes, adrenalectomy (ADX) and dexamethasone (DEX) administration, respectively. Infusion of IL-1beta i.c.v., even in doses as low as 0.1 microg/day, induced significant increases in plasma ACTH and B levels. HPX and ADX rats died within 18 h after starting the IL-1beta infusion (0.5 microg/day). Immunoneutralization of CRH significantly decreased and macrophage depletion significantly increased the stimulation of the HPA axis by IL-1 (4.0 microg/day). Administration of high doses of DEX completely abolished the stimulation of the HPA axis by IL-1beta (2.0 microg/day). The present study demonstrates that lower doses of IL-1beta were able to activate the HPA axis when infused i.c.v. compared with i.p. Regarding stimulation of the HPA axis by chronic i.p. infusion of IL-1beta the present study: (1) provides evidence that the CRH system is involved; (2) provides no evidence for a direct stimulatory effect of IL-1beta on the release of B by the adrenal gland which is of sufficient magnitude to resist the stress of chronic i.p. IL-1beta infusion; (3) shows that endogenous macrophage-derived mediators, induced by i.p. IL-1beta infusion, express an overall inhibitory rather than a stimulatory effect on the activity of the HPA axis; (4) demonstrates that exogenous administration of DEX blocks the effect of IL-1beta, which fits well in the concept of an immunoregulatory feedback between IL-1beta and glucocorticoids.
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PMID:Chronic stimulation of the hypothalamus-pituitary-adrenal axis in rats by interleukin 1beta: central and peripheral mechanisms. 905 Jul 49

The steroidogenic acute regulatory protein (STAR) participates in steroidogenesis through the mitochondrial transfer of cholesterol to cytochrome P450scc. The rat adrenal Star gene is transcribed as a 3. 5-kilobase pair (kb) and 1.6-kb mRNA with the larger mRNA predominating ( approximately 85% of total) in vivo. Hypophysectomy (HPX) produced a 3-5-fold decrease in Star mRNA along with a loss of adrenal steroids, whereas P450scc mRNA decreased by less than 2-fold. Adrenocorticotropic hormone (ACTH) treatment of HPX rats maximally stimulated steroidogenesis rates within 5 min with over 10-fold elevation of steady state blood levels occurring within 10 min. For intact rats there was a 5-10-fold larger increase, paralleling previously observed elevations of cholesterol-cytochrome P450scc association and metabolism in subsequently isolated adrenal mitochondria. ACTH did not increase either total STAR protein or a group of modified forms until at least 30 min after completion of acute stimulation, indicating that elevated translation of STAR protein cannot alone mediate this acute stimulation. Parallel slow changes in STAR protein and corticosterone formation after ACTH treatment are consistent with participation of STAR forms as co-regulators of these hormonal responses. ACTH stimulation of HPX rats increased Star mRNA by 2.5-fold within 20 min and by 4.5-fold after 1 h, thus preceding the rise in the STAR protein. A 3.5-kb Star cDNA clone isolated from a rat adrenal cDNA library exhibited a 0.9-kb open reading frame and a 2.5-kb 3'-untranslated region (3'-UTR). The open reading frame sequence differed at only 12 amino acids from that of the mouse Star. The rat Star gene seven exons with exon 7 encoding the entire 2.5 kb of 3'-UTR of the 3.5-kb mRNA. The 3'-UTR sequence suggests that 1.6- and 3.5-kb mRNA are formed by an alternative usage of different polyadenylation signals. Multiple UUAUUUA(U/A)(U/A) motifs also suggest additional regulation through this extended 3'-UTR. Although elevation of STAR protein by ACTH does not cause the acute increase in adrenal cholesterol metabolism, changes in the turnover or distribution of an active STAR subfraction cannot be excluded.
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PMID:Characterization of the rat Star gene that encodes the predominant 3.5-kilobase pair mRNA. ACTH stimulation of adrenal steroids in vivo precedes elevation of Star mRNA and protein. 951 65

Vitronectin is a multifunctional plasma glycoprotein which may regulate the systems related to protease cascades such as the coagulation, fibrinolysis, and complement systems as well as cell adhesion. Solid-phase assays and affinity chromatography on immobilized glycolipids indicated that vitronectin purified under denaturing conditions bound to sulfatide (Gal(3-SO4)beta1-1ceramide), cholesterol 3-sulfate, and various phospholipids, but not gangliosides. Only the unfolded or multimeric form of vitronectin bound to sulfatide, suggesting a conformational dependency of the binding activity, while vitronectin bound to cholesterol 3-sulfate regardless of its conformational state. The recombinant domains of human vitronectin and mutants with certain domains deleted were separately expressed in E. coli as fusion proteins. Using the recombinants, sulfatide-, phosphatidylserine-, cholesterol 3-sulfate-, Type I collagen-, heparin-, and beta-endorphin-binding activities were found to be attributable to hemopexin domain 2 and hemopexin domain 1. The possibility was suggested that the presence of a somatomedin domain and/or connecting region flanking hemopexin domain 1 inactivated its heparin binding. De-N-glycosylation of plasma vitronectin significantly affected the cholesterol sulfate- and collagen-binding activities, although its effects were opposite. These findings suggest that diverse ligand-binding activities could be attributed to pexin family motifs but that the interdomain interactions and glycosylations modulate the ligand binding activities of vitronectin.
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PMID:Characterization of the ligand binding activities of vitronectin: interaction of vitronectin with lipids and identification of the binding domains for various ligands using recombinant domains. 957 50