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 hypothesis that blood-borne beta-endorphin modulates nociception was examined with corticotropin-releasing factor (CRF) as a potent and selective agent to stimulate its release from the pituitary gland. Intravenously administered CRF produced a dose-related antinociception in rats as determined by measuring paw-lick latencies on a 50 degrees C hot plate. A dose of 25 nmol/kg of CRF was comparable in both magnitude and duration of antinociception to a 7,500 nmol/kg (= 2.5 mg/kg) dose of morphine sulfate. The antinociceptive effect of CRF was blocked by both hypophysectomy and dexamethasone pretreatment, suggesting that it was mediated by hormone release from the anterior pituitary corticotrophs. Furthermore, the effect of CRF was antagonized by 1) naltrexone, 2) naltrexone methyl bromide, and 3) passive immunization with anti-beta-endorphin antiserum. Together, these data support the hypothesis that opiate-active, beta-endorphin, released by pituitary corticotrophs, participates in the physiological modulation of nociception in rats.
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PMID:The role of pituitary beta-endorphin in mediating corticotropin-releasing factor-induced antinociception. 213 76

The influence of micelles of sodium dodecyl sulfate, cetyltrimethylammonium bromide, lysophosphatidylcholine and dodecylphosphorylcholine on the content and stability of the ordered structure of human beta-endorphin and its 12-26 fragment has been investigated. The structure was determined by far-ultraviolet circular dichroism and the stability by the resistance of the polypeptide to proteolysis with trypsin and chymotrypsin, monitored by HPLC. The alpha-helix inducing effects of the amphipathic compounds were in the order anionic greater than zwitterionic greater than cationic. The protection against proteolysis was very marked, especially for trypsin, and it was proportional to the alpha-helix inducing potential of amphipathic compounds. However, the lower resistance to proteolysis of the highly structured 12-26 fragment suggests that factors other than secondary structure may be responsible for the resistance to proteolysis.
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PMID:Circular dichroism and proteolysis of human beta-endorphin in surfactant and lipid solutions. 214 Dec 84

Mapping of the brainstem regions sensitive to beta-endorphin and morphine for antinociception and Met-enkephalin release was performed in rats. Antinociception was assessed by the tail-flick test in pentobarbital-anesthetized rats and the release of immunoreactive Met-enkephalin from the spinal cord was measured by lumbar-cisternal perfusion in urethane-anesthetized rats. The sites in the brainstem most sensitive to beta-endorphin (2 micrograms) for inhibition of the tail-flick response and Met-enkephalin release were located in areas in the caudal medial medulla such as raphe obsacurus nucleus and raphe pallidus nucleus and the adjacent midline reticular formation. Sites in the rostral medial medulla were less sensitive to beta-endorphin for both antinociception and release of Met-enkephalin. The regions 1 mm and more lateral to the midline were not sensitive to beta-endorphin. The sites sensitive to morphine sulfate (4 micrograms) for antinociception were located in areas in the rostral ventromedial medulla such as raphe magnus nucleus, gigantocellular reticular nucleus and gigantocellular reticular nucleus alpha. Raphe obscurus nucleus, which was sensitive to beta-endorphin, was not sensitive to morphine for antinociception. Locus coeruleus was sensitive to morphine and beta-endorphin for antinociception. No sites sensitive to morphine were found for Met-enkephalin release. The correlation between the brainstem sites sensitive to beta-endorphin for the production of antinociception and the release of Met-enkephalin suggests that the antinociception induced by beta-endorphin is mediated by the release of Met-enkephalin. The findings of different brainstem sites sensitive to beta-endorphin and morphine support the hypothesis of different modes of pharmacological actions for beta-endorphin and morphine.
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PMID:Brainstem sites differentially sensitive to beta-endorphin and morphine for analgesia and release of met-enkephalin in anesthetized rats. 214 38

Alterations in the circadian time structure of the secretion of several hormones were investigated in 13 male patients infected with human immunodeficiency virus (HIV). Seven were asymptomatic (classified CDC II, according to the criteria of the Atlanta Centers for Disease Control), and 6 had acquired immunodeficiency syndrome (CDC IV). Ten healthy males volunteered as controls. Plasma levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), cortisol, testosterone, ACTH, and beta-endorphin were determined by RIA in blood samples obtained every 4 h from 0830-0830 h the next morning. Data were analyzed both by two-way analysis of variance and the cosinor method. Circadian rhythms were statistically validated for each of the six hormones in each of the three groups of subjects. Compared with the control subjects, mesors (24-h adjusted means) were significantly higher for cortisol and lower for DHEA, DHEA-S, and ACTH (P less than 0.001 for all four hormones) in all HIV-infected patients. Plasma testosterone mesors were similar in controls and CDC II patients, but decreased significantly in the CDC IV patient group (P less than 0.05). Analysis of the circadian rhythms of plasma hormone levels clearly indicated an altered adrenal hormonal state in HIV-infected male patients, even during the asymptomatic period of the infection. For instance, plasma cortisol at 0430 h was more than twice as high in HIV-infected patients as it was in time-qualified controls. Although patients already had elevated plasma cortisol and lowered adrenal androgen levels at this stage, hypogonadism was not observed, as gauged by plasma testosterone concentrations. We speculate that the primary hormonal defect in HIV-infected patients is increased cortisol secretion resulting from circadian-varying stimulation of the adrenal cortex by a factor other than pituitary ACTH. This factor might be a stimulating substance secreted primarily by infected immune cells. Excess cortisol would lower adrenal androgen secretion by shifting adrenal steroid biosynthesis toward glucocorticoids and decreasing pituitary ACTH secretion via a negative feedback mechanism.
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PMID:Circadian variations in plasma levels of hypophyseal, adrenocortical and testicular hormones in men infected with human immunodeficiency virus. 230 20

In a modified Krebs buffer at 37 degrees C, the selective mu agonist [3H] D-Ala2,MePhe4,Gly-ol5]enkephalin [( 3H]DAMGO) and the nonselective mu/delta agonist human [125I]beta-endorphin [( 125I]beta-endH) bound to rat striatal membranes with a Kd of about 7 and 5 nM and a Bmax of about 95 and 260 fmol/mg of protein, respectively, consistent with labeling of mu receptors by the former ligand and labeling of both mu and delta receptors by the latter. The binding of 2 nM [125I]beta-endH was displaced by unlabeled DAMGO (IC50 30 nM), [D-Ala2-D-Leu5]enkephalin (IC50 60 nM) as well as by the selective delta agonists [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET, IC50 500 nM) and Tyr-Ala-Phe-Asp-Val-Val-Gly-NH2 (IC50 700 nM) in a monophasic manner within 2 to 3 log concentration units, suggesting an allosteric interaction between mu and delta sites labeled by [125I]beta-endH under these conditions. Accordingly, 500 nM DSTBULET caused almost 40% inhibition of the apparent Bmax without changing the apparent Kd of [3H] DAMGO. The kappa agonist U 50,488 was ineffective as competing ligand even at a concentration of 10 microM. Upon affinity cross-linking of [125I]beta-endH (2 nM) to rat striatal mu- and delta-opioid receptors, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized tissue under reducing conditions followed by autoradiography of the dried gels revealed a major broad band of covalently labeled protein with an apparent molecular weight of 80 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cross-linking of human [125I]beta-endorphin to opioid receptors in rat striatal membranes: biochemical evidence for the existence of a mu/delta opioid receptor complex. 215 52

Digitonin-solubilized opioid receptors from rat brain were purified with an affinity resin, AH-Sepharose coupled with [D-Ala2, D-Leu5]enkephalin (DADLE). Radioreceptor binding assay showed that the purified materials had specific opioid-binding activity of 310 pmol/mg protein on DADLE binding. Analyses by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) revealed that the materials were rich in two polypeptides; the major component had a molecular weight of 62000-64000. To establish the materials responsible for binding opiates, the purified materials were cross-linked with 125I-labeled beta-endorphin using bis[2-(succinimidooxycarbonyloxy)-ethyl]sulfone as a cross-linker. The molecular weight of 62000-64000, the major band of the purified materials on SDS-PAGE, agreed closely with that determined by the cross-linking experiment. The results suggest that the purified materials contained opioid-binding materials (opioid receptors).
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PMID:Identification of opioid-binding materials of rat brain. 215 52

Previous studies indicated that acute exposure of adrenal cells to adrenocorticotropic hormone (ACTH) markedly stimulates steroidogenic capacity in vitro but also inhibits cell proliferation. However, in vivo, ACTH is known to stimulate adrenal cell growth. To address this discrepancy, we determined the effect of long-term (9-11 days) continuous or intermittent exposure to ACTH on human fetal adrenal cell proliferation and steroidogenesis. Adrenal glands from fetuses 18-22 wk gestation were studied. Fetal zone cells were plated either on plastic or on an extracellular matrix (ECM) in the presence and absence of basic fibroblast growth factor (bFGF) (0.5 ng/ml) and 1 or 10 nM ACTH. As determined by cell counting, bFGF stimulated cell proliferation during 9 days in culture. In the presence of bFGF, the average doubling time decreased from 44 to 30 h on plastic and from 37 to 26 h on ECM. Under these conditions, ACTH did not inhibit cell proliferation. Proliferation of fetal adrenal corticosteroid-producing cells in the ACTH-treated cultures also was assessed by histochemical staining for 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). The number of positive cells increased more than 4-fold between Days 5 and 9 in culture. Continuous treatment with 1 nM ACTH increased dehydroepiandrosterone sulfate (DHAS) production 5- to 10-fold during the first 5 days in culture. Thereafter, the stimulated hormone production decreased over time, although there was still a difference of almost 100-fold between the control and ACTH-treated cultures at the end of 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maintenance of cell proliferation and steroidogenesis in cultured human fetal adrenal cells chronically exposed to adrenocorticotropic hormone: rationalization of in vitro and in vivo findings. 216 Dec 62

Some of the functional effects of beta-endorphin on immune cells are resistant to inhibition by naloxone. To further characterize the beta-[125I]endorphin-binding site mediating these effects and its response to cations and GTP, the human monocyte-like cell line U937 was used. Incubation of intact cells and beta-[125I]endorphin for 60 min at 4 C demonstrated a saturable, high affinity binding site [Kd = 1.2 +/- 0.5 X 10(-8) M (mean +/- SE; n = 4] competed by equimolar beta-endorphin and N-acetyl (Ac)-beta-endorphin but not by naloxone, morphine, or selective opiate receptor agonists. Competition studies showed that beta-endorphin-(6-31) and beta-endorphin-(28-31) were approximately 5- and 100-fold less potent, respectively, whereas beta-endorphin-(1-16) or -(1-27) was ineffective. Covalent cross-linking of beta-[125I]endorphin to intact cells and resolution by gel electrophoresis showed dominant bands at 59K and 44K and a minor band at 66K. The bands at 44K and 66K were completely displaced by increasing equivalent concentrations of beta-endorphin and N-Ac-beta-endorphin. Increasing concentrations of mono (Na+, K+)- and divalent (Ca2+, Mg2+, Mn2+) cations reduced the binding of beta-[125I]endorphin to U937 membrane; beta-[125I]endorphin binding to rat brain membrane showed similar cation sensitivity. GTP gamma-sulfate (GTP gamma S; 10(-4) M) alone reduced binding to U937 membrane by 25%. In the presence of Na+ (100 or 150 mM) or Mg2+ (10 mM), GTP gamma S reduced binding by an additional 50%. Moreover, GTP gamma S (10(-8)-10(-4) M) in the presence of Na+ (100 mM) reduced binding in a dose-dependent manner, whereas GMP was ineffective. In conclusion, beta-endorphin binds to sites on human U937 cells similar to those observed on normal murine splenocytes. Although naloxone insensitive, these sites exhibit properties, such as size, salt sensitivity, and coupling to a GTP-binding protein, that are similar to those observed for agonist binding to brain opiate receptors.
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PMID:Beta-endorphin binding to naloxone-insensitive sites on a human mononuclear cell line (U937): effects of cations and guanosine triphosphate. 216 44

The sexually differentiated microsomal enzyme steroid 5 alpha-reductase (NADPH: delta 4-3-oxosteroid 5 alpha-oxido-reductase, EC 1.3.99.5) catalyzes the NADPH-dependent conversion of testosterone to 5 alpha-dihydrotestosterone, a more potent androgen. In rat liver, this enzyme is expressed at a 10-fold higher level in adult females as compared to adult males. The pituitary regulation of this enzyme and its mRNA was studied in untreated and hypophysectomized rats and in rats rendered hypothyroid by treatment with the antithyroid drug methimazole. Hepatic 5 alpha-reductase activity was elevated 8-fold, to 85% of adult female levels, in adult male rats given growth hormone by continuous infusion. This same treatment was only partially effective in restoring 5 alpha-reductase in rats depleted of endogenous growth hormone by hypophysectomy, indicating that other pituitary-dependent factors contribute to the elevation observed in the inact animals. Further analysis revealed that thyroxine, but not adrenocorticotropic hormone (ACTH) or chorionic gonadotropin, could elevate 5 alpha-reductase activity and mRNA when given to the hypophysectomized rats and that this effect was enhanced by the presence of growth hormone. This thyroid hormone dependence was confirmed by the decrease in hepatic 5 alpha-reductase expression in hypothyroid rats and by its substantial restoration following thyroxine replacement. Thyroxine also stimulated expression of another female-predominant hepatic mRNA, encoding the steroid 16 alpha-hydroxylase cytochrome P-450f (IIC7), in a manner that was independent of the stimulatory effect of growth hormone on this transcript. In contrast, thyroid hormone did not significantly affect protein or mRNA levels of the growth hormone-stimulated, female-specific steroid sulfate 15 beta-hydroxylase P-450 2d (IIC12). These findings establish that thyroid hormones act at a pretranslational level to modulate the expression of some, but not all, growth hormone-stimulated hepatic mRNAs and demonstrate that both thyroxine and growth hormone can independently contribute to the sex-dependent expression of hepatic enzymes of steroid metabolism.
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PMID:Pretranslational control by thyroid hormone of rat liver steroid 5 alpha-reductase and comparison to the thyroid dependence of two growth hormone-regulated CYP2C mRNAs. 217 47

Clinical status, skin biopsy specimens, and endocrine function were evaluated in normal-coated Pomeranians (n = 12) and Pomeranians affected with growth hormone (GH)-responsive dermatosis (n = 7), then were compared with values in mixed-breed dog controls (n = 19). All Pomeranians were clinically normal; however, the Pomeranians with GH-responsive dermatosis had bilateral alopecia and hyperpigmentation of the trunk, caudal portion of the thighs, and ventral neck region. Skin biopsy specimens from the affected Pomeranians had decreased-to-normal epidermal thickness and follicular atrophy, compared with normal-coated Pomeranians. Numerous elastin fibers were observed in the skin biopsy specimens of unaffected and affected Pomeranians. Both groups of Pomeranians had normal results of thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) response, adrenocorticotropin (ACTH) stimulation, and dexamethasone suppression testing. There was no significant increase in serum GH concentration in either group of Pomeranians after xylazine or human GH-releasing factor (GHRF) administration, whereas control dogs had significant (P less than or equal to 0.05) increase in serum GH concentration after administration of either agent. Baseline plasma ACTH concentration in unaffected and affected Pomeranians was increased above the normal range (40 to 90 pg/ml). Post-ACTH administration serum progesterone, 17-hydroxyprogesterone, and androgen (dehydroepiandrosterone sulfate or androstenedione) concentrations were consistently high in unaffected and affected Pomeranians, compared with values in control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal abnormalities in Pomeranians with normal coat and in Pomeranians with growth hormone-responsive dermatosis. 217 97


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