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)

Glucocorticoids inhibit stimulus-evoked ACTH secretion by the rapid induction of new protein(s) that suppress intracellular free calcium signals. The present study examined whether the calcium receptor protein, calmodulin, is induced by glucocorticoids in the mouse pituitary corticotrope tumor (AtT20 D16:16) cell line. Treatment of AtT20 D16:16 cells with the synthetic glucocorticoid dexamethasone markedly (up to 10-fold) increased the level of a single (approximately 1.6kb) calmodulin mRNA 90 min after the application of steroid. Puromycin applied 15 min before and during dexamethasone treatment blocked the induction of this mRNA, suggesting that additional glucocorticoid induced transcription factor proteins may be required for enhanced calmodulin gene transcription. A two-fold increase in the intensity of an approximately 18K immunoreactive calmodulin protein band was detected by immunoblotting at 90 min after dexamethasone administration. Corticotropin releasing factor, added for 30 min at the start of steroid treatment, prevented the increase of calmodulin mRNA, as well as the suppression of corticotropin releasing factor-evoked ACTH release caused by dexamethasone. These data suggest that calmodulin may be involved in the early phase of glucocorticoid inhibition of pituitary ACTH release.
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PMID:Early glucocorticoid induction of calmodulin and its suppression by corticotropin-releasing factor in pituitary corticotrope tumor (AtT20) cells. 133 64

The pathophysiologic effects of cocaine on neuronal, pulmonary, and cardiovascular tissue are related to the drug's interaction with select catecholamine and neuroendocrine systems. Cocaine has been shown to alter circulating levels of the neurotransmitters, dopamine, norepinephrine, epinephrine, as well as the hypothalamic-pituitary-adrenal axis hormones corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Furthermore, brain and lung tissue have been identified as primary sites of cocaine sequestration and metabolism. This paper reviews evidence suggesting that steroid-potentiated actions of catecholamines on vascular tissues contributes to the etiology of cocaine-related medical complications, including ischemic stroke, coronary ischemia, and ischemia-based renal failure.
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PMID:Brain, lung, and cardiovascular interactions with cocaine and cocaine-induced catecholamine effects. 133 74

It has been reported that cells of the immune system produce and release considerable amounts of pro-opiomelanocortin (POMC) -derived peptides in response to coculture with a variety of stimulatory agents. The present study investigated whether extracts of human peripheral blood mononuclear cells (PBMC) contain immunoreactivity for beta-endorphin (beta E) and related peptides. Using four endorphin RIA systems with different specificities, extracts of freshly isolated PBMC and PBMC cultured in the presence or absence of mitogens or of corticotropin releasing factor (CRF) and vasopressin (VP), were analyzed. With a radioimmunoassay (RIA) system directed to the midportion of beta E, immunoreactivity (MP beta E-IR) was readily detectable, although the concentration was extremely low (ca. 200 pg/10(7) cells). beta E immunoreactivity (beta E-IR) and alpha-endorphin immunoreactivity (alpha E-IR), as determined in C-terminally directed RIA systems, were present in even lower concentrations. gamma-Endorphin immunoreactivity (gamma E-IR) was hardly detectable. Of subsets enriched in T-cells, B-cells or monocytes, the highest concentration of MP beta E-IR was detected in extracts of monocytes. Coculture of PBMC with the mitogen Concanavalin A (Con A) or Phytohaemagglutinin (PHA) increased the amount of MP beta E-IR in extracts of the cells. No increase in alpha E-IR, however, was detected, whereas beta E-IR was only increased in extracts of cells cultured in the presence of Con A. No increase, in any of the immunoreactivities, was observed in extracts of PBMC cultured with bacterial lipopolysaccharide (LPS) or with the combination of CRF and VP, both stimuli that have been reported to induce POMC peptides in cultured PBMC. The present data show that human PBMC contain endorphin-like immunoreactivity, but in very small amounts. The extremely low concentrations and the ineffectiveness of LPS and the combination of CRF and VP to increase the endorphin-like immunoreactivity raise questions about the reported capacity of PBMC to synthesize POMC-derived peptides.
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PMID:Endorphin-like immunoreactivities in uncultured and cultured human peripheral blood mononuclear cells. 137 Nov 79

Previous studies have identified a group of cells in the dorsolateral hypothalamus that project to many different areas in the CNS, such as thalamus, diagonal band of Broca, basal ganglia, cerebral cortex, hippocampus, and olfactory bulb. Their role is presently unknown, but the cells have been reported to stain for an intriguing array of putative neurotransmitter-related substances, including alpha-melanocyte-stimulating hormone (alpha MSH), melanin-concentrating hormone (MCH), human growth-hormone-releasing factor 1-37 (hGRF 1-37), corticotropin-releasing factor (CRF), metorphamide, and acetylcholine esterase. A monoclonal antibody produced in the present study, alpha C11, stains both the cell bodies of this system in hypothalamus, with a punctate pattern, and varicose fibers in the various target areas. In double-label immunocytochemical experiments in rat DLH, alpha C11 and MCH staining exactly overlaps. Concentrations of alpha MSH and MCH high enough to completely block staining with the corresponding antisera had no effect on staining with alpha C11. Similarly, CRF, hGRF 1-37, and metorphamide were unable to block alpha C11 staining. The results suggest that the antigenic epitope for alpha C11 is not contained in alpha MSH, MCH, CRF, hGRF, or metorphamide, and thus, that alpha C11 is detecting another antigen uniquely expressed in these neurons. The punctate appearance of staining in the hypothalamus and the concentration of staining in fiber varicosities suggests that the alpha C11 epitope may be involved in synaptic function.
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PMID:Novel antigenic determinant expressed in neurons of the dorsolateral hypothalamus in rat and human. 137 80

Electrophysiologic studies support the hypothesis that corticotropin-releasing factor, the neurohormone that initiates adrenocorticotropin release during stress, also serves as a neurotransmitter in the pontine noradrenergic nucleus, the locus coeruleus. To elucidate the circuitry underlying proposed corticotropin-releasing factor neurotransmission in the locus coeruleus, the present study utilized immunohistochemical techniques to characterize corticotropin-releasing factor innervation of rat locus coeruleus and pericoerulear regions. Corticotropin-releasing factor-like immunoreactive fibers were identified in the locus coeruleus of colchicine- and non-colchicine-treated rats. However, corticotropin-releasing factor innervation of pericoerulear regions rostral and lateral to the locus coeruleus was more dense than that of the locus coeruleus proper. Double-labeling studies utilizing antisera directed against corticotropin-releasing factor and tyrosine hydroxylase indicated that corticotropin-releasing factor-like immunoreactive fibers overlap with tyrosine hydroxylase-like immunoreactive processes of locus coeruleus neurons, particularly in rostral medial and lateral regions. A group of corticotropin-releasing factor-like immunoreactive neurons was localized just lateral to the locus coeruleus and numerous corticotropin-releasing factor-like immunoreactive neurons were visualized just ventral to the rostral pole of the locus coeruleus in a region corresponding to Barrington's nucleus. None of these corticotropin-releasing factor-like immunoreactive neurons were tyrosine hydroxylase-positive. To determine the source of corticotropin-releasing factor-like immunoreactive fibers in the locus coeruleus, injections of the retrograde tracer [wheat germ agglutinin conjugated to inactivated (apo) horseradish peroxidase coupled to gold particles] were made into the locus coeruleus and sections were processed for corticotropin-releasing factor-like immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Corticotropin-releasing factor innervation of the locus coeruleus region: distribution of fibers and sources of input. 137 57

Corticotropin-releasing hormone (CRH), somatostatin (SOM), delta-sleep-inducing peptide (DSIP), neuropeptide Y (NPY), beta-endorphin (beta-END), and vasopressin (AVP), which are regarded as being involved in the HPA-regulation were investigated in lumbar CSF of 44 suicide attempters. The patients were diagnosed according to the DSM-III-R, and rated with the MADRS. The neuropeptides were compared with the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in CSF and with post-dexamethasone plasma cortisol. We found strong correlations between CRH and the peptides SOM and beta-END. The latter also correlated positively with SOM. There were no differences between men and women. Patients with major depressive disorders had significantly lower SOM, CRH, and DSIP than other patients. Both SOM and beta-END correlated negatively with post dexamethasone plasma cortisol in all patients. We found no significant relationships between neuropeptides and CSF 5-HIAA. Patients who had made previous suicide attempts had significantly lower CRH than those who had not. No other significant associations between neuropeptides and suicidal subgroups of patients appeared, and there was no indication of specific neuropeptide patterns in patients who later completed suicide. Intercorrelations of some neuropeptides and low SOM and DSIP in major depressed patients are findings in line with those by others.
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PMID:HPA-related CSF neuropeptides in suicide attempters. 137 70

Six groups of adrenal glands from 17-day fetal rats were explanted to organ culture for 2 days. In one group, adrenal gland was cultured alone, and in the remaining five groups adrenal gland was cultured with pituitaries from fetuses ranging in age from 14 to 18 days. In each of the groups, half of the cultures had corticotropin-releasing factor (CRF) added to the medium. A histometric parameter utilized the size of adrenocortical cells as an indicator of sensitivity of the pituitary-adrenal system. When 17-day adrenal gland was cultured alone, addition of CRF did not cause any enlargement of cortical cells. When the adrenal gland was cultured with two 14-day pituitaries, cortical cells were enlarged. Addition of CRF to this culture induced no further change. With two 15-day pituitaries in the presence of CRF, cortical cells were slightly larger than those in the absence of CRF. With 16- to 18-day pituitaries, a marked hypertrophy of cortical cells was induced, and the addition of CRF caused further acceleration in their enlargement. These results suggest that, in organ culture, 14-day pituitary can release some adrenocorticotropic hormone (ACTH) with or without additional CRF. Older pituitaries (16- to 18-day) can apparently release an amount of ACTH in the presence of CRF that is greater than their own spontaneous ACTH secretion.
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PMID:Sensitivity of the fetal rat pituitary-adrenal system to corticotropin-releasing factor in organ culture. 141 17

The molecular and biochemical bases for interactions between the immune and central nervous systems are described. Immune cytokines not only activate immune function but also recruit central stress-responsive neurotransmitter systems in the modulation of the immune response and in the activation of behaviors that may be adaptive during injury or inflammation. Peripherally generated cytokines, such as interleukin-1, signal hypothalamic corticotropin-releasing hormone (CRH) neurons to activate pituitary-adrenal counter-regulation of inflammation through the potent antiinflammatory effects of glucocorticoids. Corticotropin-releasing hormone not only activates the pituitary-adrenal axis but also sets in motion a coordinated series of behavioral and physiologic responses, suggesting that the central nervous system may coordinate both behavioral and immunologic adaptation during stressful situations. The pathophysiologic perturbation of this feedback loop, through various mechanisms, results in the development of inflammatory syndromes, such as rheumatoid arthritis, and behavioral syndromes, such as depression. Thus, diseases characterized by both inflammatory and emotional disturbances may derive from common alterations in specific central nervous system pathways (for example, the CRH system). In addition, disruptions of this communication by genetic, infectious, toxic, or pharmacologic means can influence the susceptibility to disorders associated with both behavioral and inflammatory components and potentially alter their natural history. These concepts suggest that neuropharmacologic agents that stimulate hypothalamic CRH might potentially be adjunctive therapy for illnesses traditionally viewed as inflammatory or autoimmune.
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PMID:The stress response and the regulation of inflammatory disease. 141 62

In addition to their characterizing secretory products, both magnocellular and parvocellular neurosecretory neurons are now known to express other neuroactive substances. Parvocellular neurons that make corticotropin-releasing factor (CRF) for example are capable of synthesizing at least seven neuropeptides. Some of these, like arginine vasopressin (AVP), interact with CRF at the level of the anterior pituitary to promote corticotropin secretion, and, like CRF, are regulated negatively by glucocorticoids and positively by at least some stressors. others are inert in these two contexts but are responsive to various challenges. Magnocellular neurosecretory oxytocin- and AVP-containing neurons are capable of producing similarly broad and distinctive complements of neuroactive principles. These are typically expressed at levels far lower than those of the nonapeptides, suggesting local modulatory effects on oxytocin and/or AVP secretion at the level of the posterior lobe. Differential regulation of coexisting molecules within magnocellular neurons by systemic challenges and steroid hormones has also been described. Secretory products of magnocellular neurons may gain access to the anterior pituitary via exocytotic release at the level of the median eminence or through vascular links between the posterior and anterior lobes, suggesting another form of 'co-localization' by which the two neurosecretory cell types may interact in the control of stress and perhaps other pituitary-mediated responses.
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PMID:Co-localization of neuroactive substances in the endocrine hypothalamus. 142 23

The human placenta has been implicated as a source of numerous peptide hormones during pregnancy. Since the immunoassay detection of the proopiomelanocortin derived peptide beta-endorphin (beta E) in placental extracts in 1978, it has remained uncertain whether placental beta E immunoreactivity (IR) is 1) secreted into the maternal circulation and 2) opiate receptor active during pregnancy. To elucidate the nature of beta E IR in the placenta, both beta E IR and N-alpha-acetylated beta E (Ac beta E) IR were simultaneously measured in extracts of human pituitaries, placentas, and plasma by two homologous RIAs. Pituitary extracts (n = 6) contained 38 +/- 7 nmol beta E IR per g wet wt tissue (mean +/- SEM), of which only 20 +/- 4 pmol/g were Ac beta E IR. Term placental extracts (n = 19) had 201 +/- 30 fmol/g wet wt total beta E IR and 30 +/- 3 fmol/g wet wt total Ac beta E IR, which comprised 15% of total beta E IR in placental extracts. Total plasma beta E IR rose from 28 weeks gestation (8.5 +/- 0.3 fmol/mL, n = 159) to peak at labor (50 +/- 4 fmol/mL, n = 98; P < 0.01) but total Ac beta E IR was found in only four 28-week (1.7 +/- 0.9 fmol/mL) and 42 labor plasma samples (0.9 +/- 0.1 fmol/mL). Gel filtration chromatography of placental and pituitary extracts showed that while less than 1% of the beta E31-size material was acetylated in the pituitary, up to 60% of the beta E31-size material in placental extracts was acetylated. In pooled third trimester plasma extracts, however, only 4% of the beta E31-size material was acetylated. Furthermore, the ratio of beta E31:beta-lipotropin in pituitary extracts (n = 3) was 0.5; pooled plasma-0.5, and placental extracts (n = 5)-1.2. These data indicate that 1) the placenta extensively N-alpha-acetylates beta E31 destroying its opiate bioactivity while the pituitary does not; 2) beta E IR in pregnant women's plasma is similar to pituitary beta E IR, being mostly nonacetylated and similar in size to beta-lipotropin. These findings are consistent with a pituitary source for the elevated plasma beta E IR found during late pregnancy which may, in turn, be a consequence of elevated plasma concentrations of placentally secreted plasma corticotropin-releasing factor IR present during the third trimester.
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PMID:Beta-endrophin immunoreactivity during human pregnancy. 146 47


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