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)

alpha-Melanocyte stimulating hormone (alpha-MSH), a peptide derived from POMC has previously been shown to antagonize the action of exogenously administered beta-endorphin (beta-EP) on pituitary PRL and LH release in the primate. In this study, we have tested the ability of alpha-MSH to block some of the acute pituitary effects of CRF and interleukin-1 alpha (IL-1 alpha), effects which are thought in part to result from the release of endogenous beta-EP. Experiments were performed in ovariectomized rhesus monkeys bearing a chronically implanted lateral ventricular cannula for peptide infusion. Peripheral blood samples for LH, cortisol, and PRL RIA were obtained at 15-min intervals during a 3-h control period when saline was infused into the ventricle, followed by a 5-h experimental period. CRF (15 micrograms/h) infused alone for 5 h caused a significant suppression of pulsatile LH release; by the fifth hour, LH secretion was reduced to 32.5 +/- 2.4% of the control saline infusion. The CRF-induced suppression of LH was prevented by coinfusion of alpha-MSH (60 micrograms/h); by the fifth hour LH was 89.0 +/- 3.6% of the control (P less than 0.05 vs. CRF alone). alpha-MSH also prevented the CRF-induced decrease in LH pulse frequency (P less than 0.05). IL-1 alpha (4.2 micrograms) was infused alone for 30 min or in combination with alpha-MSH (120 micrograms/h for 2 h). After IL-1 alpha alone, LH decreased to 30.1 +/- 2.4% of baseline at 5 h. This decrease was prevented by alpha-MSH; by 5 h LH was 101 +/- 5.1% of baseline (P less than 0.005 vs. IL-1 alpha alone). IL-1 alpha did not affect LH pulse frequency but pulse amplitude was reduced; this reduction was prevented by alpha-MSH (P less than 0.05). IL-1 alpha also stimulated PRL release. PRL rose from a mean baseline of 3.5 +/- 0.3 ng/ml to a peak of 13.8 +/- 2.7 ng/ml; after coinfusion of alpha-MSH the mean peak PRL response was only 4.4 +/- 1.5 ng/ml (P less than 0.001 vs. IL-1 alpha alone). After CRF infusion, cortisol increased to 136 +/- 7.9% of the mean morning baseline concentration. This increase was not prevented by alpha-MSH coinfusion; after CRF plus alpha-MSH, cortisol increased to 121 +/- 6.0% of baseline. In contrast, alpha-MSH prevented the IL-1 alpha-induced increase in cortisol: 167 +/- 15.5% vs. 91.7 +/- 8.3% (P less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alpha-melanocyte-stimulating hormone antagonizes the neuroendocrine effects of corticotropin-releasing factor and interleukin-1 alpha in the primate. 131 15

We have investigated the effects of recombinant human interleukin (IL)-1 alpha, IL-1 beta and IL-6 on the activation of the hypothalamo-pituitary-adrenal axis. We have determined the effects of a single i.p. injection of cytokine on circulating ACTH and corticosterone levels, corticotrophin-releasing factor (CRF) mRNA in the parvocellular cells of the paraventricular nucleus and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary at both 4 h and 24 h after injection. IL-1 alpha had no effect on any of the parameters measured at either time-point. In contrast, IL-1 beta increased CRF mRNA in the parvocellular paraventricular nucleus and POMC mRNA in the anterior pituitary 4 h after injection. Plasma ACTH and corticosterone were increased at 4 h and circulating ACTH was still increased at 24 h after treatment with IL-1 beta. IL-6 had no effect on message levels but did increase circulating ACTH and corticosterone levels both 4 h and 24 h after injection. The mechanism responsible for the increase in circulating ACTH after IL-6 injection is unclear but would appear to be different from that which is activated by IL-1 beta which also results in increased CRF and POMC gene expression.
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PMID:The effects of recombinant human interleukin (IL)-1 alpha, IL-1 beta or IL-6 on hypothalamo-pituitary-adrenal axis activation. 131 53

The pattern of expression of at least four neuropeptides contained in adrenomedullary chromaffin cells is altered by exposure to the cytokines interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF alpha), alone or in combination with stimulation of other second messenger pathways. Vasoactive intestinal polypeptide (VIP) was elevated 2- to 3-fold by 1 nM IL-1 alpha within 48 h of exposure, while neurotensin and substance P synthesis were unaffected, and met-enkephalin levels were decreased 25-35%. Stimulation of VIP and substance P biosynthesis by forskolin was markedly enhanced by IL-1 alpha, while forskolin stimulation of enkephalin and neurotensin biosynthesis was unaffected. IL-1 alpha amplified the effect of phorbol myristate acetate to increase the VIP content of chromaffin cells, but antagonized phorbol ester-induced elevation of neurotensin levels. TNF alpha also demonstrated a neuropeptide-specific pattern of modulation of second-messenger effects on chromaffin cell neuropeptide levels similar to those seen with IL-1 alpha. The neuroendocrine actions of IL-1 alpha described above, unlike IL-1 action in the immune system, do not appear to be mediated through IL-2 as this cytokine did not affect VIP or enkephalin expression in the presence or absence of protein kinase stimulation. Neither IL-1 alpha nor TNF alpha affected the calcium-coupled stimulation of neuropeptide secretion and biosynthesis that occurs in response to cell depolarization in these and other neuroendocrine cells in vitro and in vivo. These data provide a functional demonstration of IL-1 and TNF receptors in chromaffin cell cultures and suggest a physiological role for cytokine production in the adrenal medulla. Since both the magnitude and direction of neuropeptide synthesis modulation by IL-1 alpha and TNF alpha are highly peptide-specific, it appears that these cytokines do not merely augment second messenger pathways that affect neuropeptide synthesis, but potentially regulate the activity of factors controlling the pattern of neuropeptide gene expression in chromaffin cells.
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PMID:Interleukin-1 alpha and tumor necrosis factor-alpha differentially regulate enkephalin, vasoactive intestinal polypeptide, neurotensin, and substance P biosynthesis in chromaffin cells. 137 39

This in vitro study examined the effects of interleukin-1 (IL-1) and interferon-gamma (Ifn-gamma) on the release of cholecysto-kinin (CCK) from superfused hypothalamo-neurohypophyseal complexes (HNC) of rats. An increase of CCK from HNC was elicited in a dose-dependent manner by recombinant human IL-1 alpha and -1 beta in concentrations of 0.1-10 nM. In contrast, the release of CCK from HNC was not affected by recombinant human Ifn-gamma at any dose tested (0.1, 1 and 10 nM). The increased release of CCK elicited by IL-1 was calcium-dependent, as was that induced by potassium (60 mM), but it was biphasic and had a different time course and a lower magnitude than those induced by potassium and veratridine. These results suggest that IL-1 activates pituitary-adrenal axis by stimulating CCK neurons in the hypothalamus and/or neurohypophysis to release CCK, since CCK has been implicated in the regulation of adrenocorticotropin release.
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PMID:Stimulation of cholecystokinin (CCK) release from superfused rat hypothalamo-neurohypophyseal complexes by interleukin-1 (IL-1). 145 18

Interleukin-1 (IL-1) and interleukin-6 (IL-6) share a number of biological functions. Because IL-1 induces IL-6 in vivo, the extent to which IL-6 mediates the effects of IL-1 has come under investigation. The stimulation of the hypothalamic-pituitary-adrenal axis by IL-1 and IL-6 is a critical component of the inflammatory response. The present study was designed to compare the effects of recombinant human IL-1 alpha (rhIL-1 alpha) and recombinant human IL-6 (rhIL-6) administered in combination and alone on the release of adrenocorticotropic hormone (ACTH) in mice. We have demonstrated that the administration of rhIL-6 alone does not duplicate the stimulatory effect of rhIL-1 alpha on ACTH release. On the other hand, suboptimal amounts of rhIL-1 alpha and rhIL-6 synergize to induce an early (30-60 min) ACTH response and produce a later (2-3 h) response that is similar to the one observed after rhIL-1 alpha is administered alone. These results suggest that the 2-3 h response to rhIL-1 alpha may be dependent on synergy with the endogenous IL-6 it induces systemically and in the central nervous system (including the hypothalamus and the pituitary gland).
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PMID:Interleukin-1 and interleukin-6 act synergistically to stimulate the release of adrenocorticotropic hormone in vivo. 165 67

Utilizing push-pull perfusion, we examined secretory profiles of corticotropin releasing hormone (CRH) in the median eminence (ME) and of plasma adrenocorticotropin (ACTH) in freely moving male rats after intravenous bolus injection of recombinant human interleukin (IL)-1 alpha (1.0 microgram) and 1 beta (1.0 microgram). The ME was perfused with artificial cerebrospinal fluid between 11.00 and 14.00 h, and perfusates and blood samples were collected every 20 min. Administrations at 12.00 h of IL-1 alpha and 1 beta, but not vehicle only, resulted in significant increases in both the plasma ACTH and ME-CRH. The rise in ME-CRH clearly preceded the enhanced ACTH secretion. These in vivo data strongly suggest that IL-1 stimulates ACTH secretion, at least in part, by triggering hypothalamic CRH release. This is the first to characterize the temporal profile of CRH secretion in the ME after intravenous administration of IL-1 to freely moving rats.
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PMID:Evidence that intravenous administration of interleukin-1 stimulates corticotropin releasing hormone secretion in the median eminence of freely moving rats: estimation by push-pull perfusion. 166 17

We have studied the effects of natural opioids on interleukin-1 (IL-1) -induced interleukin 2 (IL-2) production by the lymphoid cell line EL-4. beta-Endorphin (beta-end) significantly enhanced IL-2 production by IL-1-stimulated EL-4 cells. Similar results were obtained using the LBRM33-1A5 cell line. beta-End induced significant enhancement (35-100%) of IL-1-induced IL-2 production at all concentrations of IL-1 tested (2-0.25 U/ml) and the effects were seen with both IL-1 alpha and IL-1 beta. The dose response of beta-end augmentation of IL-1-induced IL-2 production was bimodal, with peak activities seen at high (10(-8)-10(-10) M) and low (10(-16) M) beta-end concentrations. The specificity of beta-end effect was studied using the opioid antagonist naloxone. Naloxone completely abolished the enhancing effects of beta-end, indicating that the effects might be mediated through binding to opioid receptors. In addition, other opioid peptides, including gamma-endorphin and enkephalins, elicited similar effects. Northern blotting analysis revealed higher levels of IL-2 mRNA in beta-end-treated IL-1-induced EL-4 cells than in IL-1-induced control cells. Thus, beta-end might enhance IL-2 production by either augmenting the transcription rate or increasing IL-2 mRNA stability. These results suggest that beta-end might play an important role in the regulation of lymphokine production in the periphery in addition to its known interactions with IL-1 in the central nervous system.
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PMID:Beta-endorphin modulation of IL-1-induced IL-2 production. 168 7

1. This study demonstrates that human recombinant interleukin-1 (IL-1) stimulates beta-endorphin release and potentiates the secretion of beta-endorphin in both a mouse anterior pituitary cell line AtT-20 and rat pituitary cell cultures. 2. In pituitary cell cultures, prolonged treatment with phorbol ester had no effect on IL-1-induced beta-endorphin release, but abolished the potentiating effects of IL-1 on vasopressin-induced beta-endorphin secretion. 3. The enhancement of CRF-stimulated beta-endorphin release by IL-1 was also reduced in normal pituitary cell cultures following depletion of protein kinase C. 4. The late IL-1-induced secretion of beta-endorphin does not require the continuous presence of the cytokine. 5. Incubation of monolayers with 125I-IL-1 alpha (10(-9) M) at 8 degrees C and then at 37 degrees C for various times revealed that IL-1 alpha was internalized. There was a progressive increase in the ratio of cytoplasmic to cell-surface-associated 125I-IL-1 alpha. 6. These results indicate that the IL-1-induced beta-endorphin release and its potentiation of beta-endorphin secretion involves internalization of this cytokine, perhaps via cell surface IL-1 receptors.
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PMID:Interleukin-1 potentiation of beta-endorphin secretion and the dynamics of interleukin-1 internalization in pituitary cells. 174 31

Interleukin 1 alpha (IL-1 alpha), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. We injected recombinant human IL-1 alpha into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1 alpha caused an almost immediate reduction of plasma LH concentration; this decrease was statistically significant 20 min after injection and occurred through a highly significant reduction in the number of LH pulses, with no effect on pulse amplitude. In contrast, there was no change in pulse frequency but a small significant elevation in amplitude of FSH pulses. Intraventricular injection of the diluent had no effect on gonadotropin release. The results provide further evidence for separate hypothalamic control mechanisms for FSH and LH release. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1 alpha (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E2 into the medium was measured by RIA in the presence or absence of norepinephrine (50 microM). IL-1 alpha reduced basal LHRH release and blocked LHRH release induced by norepinephrine. It had no effect on the basal release of prostaglandin E2; however, it completely inhibited the release of PGE2 evoked by norepinephrine. To evaluate the possibility that IL-1 alpha might also interfere with the epoxygenase pathway of arachidonic acid metabolism, epoxyeicosatrienoic acids were also measured. IL-1 alpha had no effect on the content of epoxyeicosatrienoic acids in the hypothalamic fragments as measured by gas chromatography and mass spectrometry. In conclusion, IL-1 alpha suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E2-mediated release of LHRH.
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PMID:Interleukin 1 alpha inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone. 190 15

We investigated whether hypothalamic prostaglandin E2 (PGE2) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 alpha (IL-1 alpha). The present results show that ACTH responses induced by intravenous injection of IL-1 alpha were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE2 stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE2. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE2.
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PMID:ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE. 216 51


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