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 tyrosine-3-monooxygenase activity [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] of rat adrenal medulla is induced 20-24 hr after the injection of reserpine (16 mumol/kg intraperitoneally). This and other inducing stimuli increase the 3': 5'-cyclic AMP (cAMP) content in the medulla for longer than 60 min and activate the cAMP-dependent protein kinase (ATP: protein phosphotransferase; EC 2.7.1.37) for several hours. Corticotropin (ACTH), dopamine, and propranolol do not induce the monooxygenase, but elicit an increase in the cAMP content of the medulla which fails to activate protein kinase and lasts less than 1 hr. A high- and low-molecular-weight protein kinase are separated by gel filtration from the 20,000 X g pellet extract of adrenal medulla homogenate. The activity of the low-molecular-weight enzyme is expressed as its ability to phosphorylate histone. The protein kinase activity of the pellet is increased between 3 and 17 hr after reserpine injection. Our evidence indicates that this increase is due to a translocation from cytosol to subcellular structures of a kinase that utilizes lysine-rich histone as phosphate acceptor. The protein kinase activity that is extracted from a purified nuclear fraction prepared from the adrenal medulla of rats injected 7 hr previously with reserpine is greater than that extracted from medulla of saline-treated rats.
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PMID:Activation and nuclear translocation of protein kinase during transsynaptic induction of tyrosine 3-monooxygenase. 0 93

Corticotropin-Releasing Factor (CRF) activity was determined (dispersed pituitary cell assay) in rat median eminence (ME), various hypothalamic nuclei, as well as in entire median basal hypothalamus (MBH) and extra-hypothalamic areas. Highest concentrations were seen in ME, with decreased concentrations noted proceeding dorsally and cephalad from ME. Potency (NIAMDD HE-RP-1, ME reference extract, equivalent to 1.0) estimates were: ME-2.2; arcuate n.-0.88; dorsomedial n.-041; ventromedial n.-0.35; periventricular n.-0.24; hypothalamus-0.05; thalamus-0.01; cortex-0.005. Measurable, but lesser amounts, than in the above cited nuclei, were present in supraoptic and paraventricular nuclei. CRF activity was not measurable in preoptic area, septum, olfactory bulb, striatum, mesencephalon, pons, medulla or cerebellum. Complete hypothalamic deafferentation was accompanied by an increase in CRF activity/mug protein in ME and MBH, associated with decreased AM plasma ACTH and corticosterone concentrations. CRF-like activity in ME and MBH increased following hypophysectomy and after dexamethasone pretreatment. These findings indicate that CRF is mainly synthesized in the ME and surrounding area, and this source of CRF is sensitive to feedback effects and that extrahypothalamic inputs affect CRF release. Female animals had higher ME CRF content than did male animals. Homozygous and heterozygous Brattleboro rats had significantly less CRF in ME and MBH than did control animals, with significant differences also noted between homozygous and heterozygous animals.
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PMID:Corticotropin releasing factor distribution in normal and Brattleboro rat brain, and effect of deafferentation, hypophysectomy and steroid treatment in normal animals. 1 88

Experiments were conducted on male Wistar rats. A study was made of the intensity of incorporation into the liver, kidneys, the thyroid gland, the adrenal glands and the rate of elimination from the blood plasma of two ACTH preparations iodated by Greenwood's method: International Standard for Corticotropin, Mill Hill, London; Hum ACTH--Hid-28, Richter. It appeared that the preparations of natural swine -125-I-ACTH and of synthetic -131-I-ACTH were identical chromatographically and by saturation with iodine-125 and iodine-131, respectively, but differed by their behaviour in the organism. T1/2 for -125-I-ACTH (swine) was 4.7 min; the hormone was not incorporated into hepatic parenchyma, and only very weakly--into the kidneys, but it was intensively accumulated by the adrenal galnds. Radioactivity peak was recorded in the adrenal cortex 6 minutes after the administration of the labeled hormone. -131-I-ACTH (synthetic) disappeared from the blood with a falf-period of 11.2 min, was incorporated into the liver and particularly into the kidneys, and was not accumulated in the adrenal gland.
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PMID:[A comparative analysis of the behavior of two labeled ACTH preparations in the body]. 16 77

Skin allograft rejection was noticeably delayed in rats following hypophysectomy. Daily injections of hypophyseal growth hormone restored the normal reaction. Additional thymectomy had no influence on the rejection of hypophysectomized rats. In these animals growth hormone by itself had no significant influence on the graft rejection. It only restored a normal reaction when given together with thymic hormone. Corticotropin injections accelerated the allograft rejection. On this action of corticotropin thymic hormone has shown a significant inhibitory influence. The thymus was thus proved to be a synergist to growth hormone and an antagonist to corticotropin. Previous observations made with usual endocrinological test- are thus confirmed with an immunological test.
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PMID:Influence of the thymus-corticothropin-growth hormone interaction on the rejection of skin allografts in the rat. 16 68

Transitional epithelium lining rabbit urinary bladders was isolated and studied in vitro. The homogeneity of the isolated epithelium was demonstrated by light and electron microscopical monitoring as well as cell culture studies. Transitional epithelium responded to epinephrine and prostaglandin E1 (PGE1) in the presence of 2mM 1-methyl, 3-isobutylxanthine (MIX) with increases in intracellular levels of cyclic adenosine 3':5'-monophosphate (cyclic AMP). Corticotropin, aldosterone, insulin, parathyroid hormone and vasopressin were slightly but significantly stimulatory under similar conditions. Glucagon and oxytocin were not stimulatory at the concentrations tested. The effects of epinephrine and PGE1 were potentiated by 2mM MIX 20-fold or greater. The cells were slightly more sensitive to PGE1 then to epinephrine. The prostaglandin produced a noticeable response at about 10nM, while effects of epinephrine were discernible at 0.1muM. Maximal responses to both effectors were seen at about 10muM. The action of 10muM epinephrine, but not 10muM PGE1, was completely abolished by 0.1mM propranolol. Responses to combinations of epinephrine and PGE1 were additive. Cyclic AMP accumulated in the incubation medium of transitional epithelial cells exposed to epinephrine, PGE1, MIX, or combinations of the agonists. The appearance of cyclic AMP in the medium was slow compared to the rate of intracellular accumulation, but reached significant levels following prolonged stimulation.
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PMID:The effects of hormones on cyclic adenosine 3':5'-monophosphate accumulation in transitional epithelium of the urinary bladder. 17 60

Circular dichroism spectra on corticotropin1-32 and its constitutive N-, and C-terminal peptides are determined in water and trifluoroethanol under several conditions in the aromatic and peptide spectral regions. Furthermore, the effects of pH and varied mixtures of water-trifluoroethanol are examined on the corticotropin1-32 molecule. The results show that the N- and C-terminal series have a different behaviour in both aqueous and organic media. Corticotropin and the former peptides display "random" spectra in water, and alpha-helix type spectra in trifluoroethanol, while the latter have "random" spectra in both solvents. In the holopeptide corticotropin, the side chain-side chain effects, as reflected by the titration curves obtained from variations in the aromatic region, support the idea of an helical organization of part of the backbone even in aqueous solution. When going from water to trifluoroethanol corticotropin1-32 undergoes a conformational change which leads to an alpha-helix, following a linear pathway. These results, together with other observations, indicate the possible role of the conformation of corticotropin molecules in their biological life.
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PMID:Conformational studies of corticotropin1-32 and constitutive peptides by circular dichroism. 18 36

The effect of 310 courses of corticotropin, methylprednisolone, prednisone, and dexamethasone were studied in 62 patients with generalized myasthenia gravis who were poorly responsive to anticholinesterase medication and most of whom required assisted respiration. Improvement in strength and response to anticholinesterase medication occurred in 91% of the courses, and was moderate or marked in 63%. The incidence, degree, and duration of improvement appeared to be dose related. High doses of dexamethasone (20 mg orally each day for 10 days, repeated if necessary), which had 75% more glucocorticoid effect than any other regimen studied, produced the highest incidence of both improvement (100%) and moderate-to-marked improvement (75%), and the greatest duration of improvement (more than 3 months after 40% of the courses). The duration of improvement following intensive courses of any of the corticosteroids was approximately doubled by the subsequent administration of smaller doses of dexamethasone or prednisone on alternate days. Most patients with severe disease relapsed after 3 to 6 months of corticosteroid treatment, but increase in the dose of corticosteroid, and daily administration, which was more effective than alternate-day administratin, almost always again resulted in improvement. Corticotropin and corticosteroids were equally effective before and after thymectomy. High doses of corticotropin and corticosteroid produced an initial exacerbation of the disease in 80% of the courses, which was moderate or marked in 57%. Reduction in dose reduced the incidence of severe exacerbation, but did not prevent it, and also resulted in slower and less marked improvement. Withholding anticholinesterase medication did not prevent exacerbation or increase improvement, and afforded no advantage, though it was usually helpful to reduce the dose of this medication. Because of the hazard of initial exacerbation and the occurrence of other serious side effects in 15% of the patients. (bleeding ulcer, vertebral compression, aseptic necrosis of the femoral head or tibia, and subcapsular cataracts), it is recommended that corticosteroid treatment be limited to myasthenic patients who are not responding satifactorily to anticholinesterase medication, that smaller doses be employed in patients whose disease is not life threatening, and that higher doses be reserved for patients who are critically ill and are being managed, at least initially, in an intensive care unit.
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PMID:Corticotropin and corticosteroids in generalized myasthenia gravis: comparative studies and role in management. 18 90

The transfer of lipoprotein-bound cholesterol into adrenal cells was examined. Adrenal glands from unstimulated or corticotropin stimulated hypophysectomized rats were incubated with high density lipoprotein (HDL) or low density lipoprotein LDL containing radiolabeled cholesterol. The rate of transfer of labeled cholesterol from HDL into the glands was two to three times greater than from LDL. Corticotropin stimulation increased the transfer of cholesterol from HDL but not LDL. The effects of corticotropin were not dependent on subsequent cholesterol utilization for steroidogenesis. The process of cholesterol transfer from HDL was linear with time over 2 hr at 37 degrees and greatly reduced at 4 degrees. In addition, the transfer process became saturated above an HDL cholesterol concentration of 900 mug/ml. About 25% of the labeled adrenal cholesterol arising from HDL was recovered within the mitochondria. The labeled cholesterol within isolated mitochondria could undergo mitochondrial conversion to pregnenolone. Finally, the delipidated HDL apolipoproteins, apoA-I and apoA-II, when added to incubations containing less than saturating concentrations of HDL, stimulated transfer of labeled cholesterol from HDL to adrenal cells. These studies suggest that rat adrenal tissue possesses an HDL specific hormonally-responsive mechanism for accumulating extracellular cholesterol and that apoA-I and apoA-II have a significant function in the uptake process.
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PMID:Adrenal cholesterol uptake from plasma lipoproteins: regulation by corticotropin. 18 33

The time course of corticotropin-induced steroidogenesis and changes in intracellular cyclic AMP and cyclic GMP levels were investigated in isolated bovine adrenocortical cells prepared by trypsin digestion. Corticotropin produced a peak rise in cyclic AMP during the first 5 min of stimulation and enhanced steroid production after 15 min. Corticotropin also caused a decrease in cortical cyclic GMP at 5 min; this decrease in cyclic GMP reverted to a 2-3 fold increase at 15-30 min which gradually subsided by 60 min. A steroidogenic concentration of prostaglandin E2 also produced an elevation in the levels of both nucleotides, but the rise in cyclic GMP preceded the rise in cyclic AMP. These results suggest that the relative amounts of cyclic AMP and cyclic GMP, rather than the absolute levels of cyclic AMP, may be a key factor in the regulation of steroidogenesis.
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PMID:On the role of cyclic AMP and cyclic GMP in steroid production by bovine cortical cells. 18 38

Following simple homogenization, significant amounts of mitochondrial-derived, cholesterol side chain cleaving enzyme (desmolase) activity are recovered in rat adrenal 105 000 X g-supernatant fraction. Corticotropin administration enhances soluble desmolase activity, and cycloheximide potentiates this effect. The lipid droplet fraction which has no desmolase activity markedly enhances pregnenolone synthesis in the soluble desmolase preparations, presumably by supplying free cholesterol substrate. Corticotropin particularly with cycloheximide pretreatment, enhances lipid fraction activity. Thus increased cholesterol availability may largely explain the corticotropin effect on the soluble desmolase system. Since protein synthesis is required for corticotropin activity in intact mitochondria, but not in calcium-swollen mitochondria or the soluble enzyme system, the labile protein apparently required during corticotropin action may function to overcome a "barrier" which exists only in the intact mitochondria and restrains cholesterol side chain cleavage.
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PMID:On the requirement for protein synthesis during corticotropin-induced stimulation of cholesterol side chain cleavage in rat adrenal mitochondrial and solubilized desmolase preparations. 18 47


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