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)

Explants prepared from the neocortex and the fetal zone of the human fetal adrenal (gestational age 13 to 18weeks) were maintained under conditions of organ culture for 7 to 9 days during which time they were exposed to hACTH and various related peptides. Corticotrophic activity was monitored by the daily release of dehydroepiandrosterone sulfate (3beta-hydroxy-5-androsten-17-one, 3-sulfate; DHA-S) and cortisol as quantified by radioimmunoassay, hACTH (2.2 x 10(-9) - 2.2 x 10(-8)M) was the most active in sustaining steroidogenesis by both neocortical and fetocortical cells. alpha-MSH possessed similar properties but not at concentrations lower than 10(-6)M, whereas CLIP (4.4 x 10(-9) - 1.1 x 10(-7)M), the 18-39 C-terminal moiety of ACTH, was devoid of activity. Corticotrophic activity with respect to fetocortical explants appeared to be that of maintenance of function best illustrated by dehydroepiandrosterone sulfate biosynthesis, while enhancement of steroidogenesis was observed in the neocortex as manifested by cortisol release. Although not eliminating the possible existence of a specific fetal corticotrophin related to ACTH1-39, the data indicate that hACTH is capable of regulating steroidogenesis in the fetal zone which is primarily geared to the formation of dehydroepiandrosterone sulfate.
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PMID:Steroidogenic activity of hACTH and related peptides on the human neocortex and fetal adrenal cortex in organ culture. 20

It was admitted that human beta-MSH was responsible for the hyper-pigmentation observed in some syndromes associated with ACTH hypersecretion. beta-LPH was a pituitary polypeptide, containing the entire sequence of beta-MSH in its fragment 37-58, and the physiological role of which remained unknown. alpha-MSH and CLIP (Corticotrophin-like Intermediary Peptide) were thought to be specific of certain species possessing a distinct pituitary pars intermedia. Recent data give new insight upon some of these conceptions. beta-MSH seems not to exist in man; it is almost established now that plasma "Immunoreactive beta-MSH" (IR-beta-MSH) is in fact beta- and/or gamma-LPH. In chronic renal failure plasma IR-beta-MSH is elevated because of a decreased plasma disappearance rate, whereas ACTH is normal. Good evidence suggests that both LPH and ACTH are synthesized in the same pituitary cell within a common polypeptidic precursor. Endogenous peptides with morphinomimetic activity (Endorphins) have been isolated from brain and hypophysis; they are all made up of different fractions of beta-LPH-C-terminal fragment 61-91; It is likely that they represent a new class of brain neurotransmitters involved in some functions of the central nervous system, structural similarities suggest that beta-LPH may be the biosynthetic precursor of Endorphins, however such a hypothesis remains to be clearly demonstrated.
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PMID:[Recent data on the group of melanotropic and lipotropic pituitary hormones (MSH-LPH) and on the brain morphinomimetic peptides (endorphins)]. 21 12

The anatomical relationships between pro-opiomelanocortin-containing axons and serotonin neurons in the nucleus raphe dorsalis (NRD) of the rat were examined at the light microscope level with antibodies against CLIP (corticotropin-like intermediate lobe peptide), alpha-MSH (alpha-melanocyte-stimulating hormone) and serotonin. Sequential double labeling was performed with either immunofluorescence or peroxidase-antiperoxidase techniques. It was observed that the network of POMC-immunoreactive axons displayed a gradient of decreasing density from rostral to caudal levels and from dorsal to ventral parts or the NRD. The examples of close proximity between immunoreactive axons and serotonin cell bodies or dendrites were rather scarce. On the whole, the immunoreactive fibers seemed to run quasi-independently of the serotonin neurons.
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PMID:Distribution of the pro-opiomelanocortin-immunoreactive axons in relation to the serotoninergic neurons in the dorsal raphe nucleus of the rat. 166 Sep 70

The immunocytochemical distribution of CLIP (corticotropin-like intermediate lobe peptide) or ACTH(18-39), a small biologically active peptide, was examined in the human brain, using a monoclonal antibody against this peptide. Groups of CLIP-immunoreactive cell bodies, small to medium size and bipolar or triangular in shape, were found in the basal hypothalamus extending from the retrochiasmatic region to the premammillary nuclei area. Immunoreactive fibers with varicosities, terminals and "pipe shape" structures, were distributed within the hypothalamus, limbic structures, the brainstem and spinal cord nuclei, forming a particularly rich network in the hypothalamus, the preoptic area, the septal region, the amygdala and the upper brainstem periaqueductal gray matter. The above neuroanatomical observations confirm and extend previous findings in animals, strengthening even more the possibility that this peptide may be involved in numerous behavioral, autonomic and physiological functions such as regulation of sleep-waking cycle, pain control and respiratory and cardiovascular regulation.
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PMID:Immunohistochemical distribution of corticotropin-like intermediate lobe peptide (CLIP) immunoreactivity in the human brain. 184 84

Apomorphine (Apo), a D1/D2 Dopamine (DA) agonist, at high doses (500 micrograms/kg) induces a short-lasting insomnia, antagonized by a secondary injection of corticotropin-like intermediate lobe peptide (CLIP, 10 ng); these effects are also observed with hypophysectomized (hypoX) rats. The administration of the serotonin (5-HT) agonist 8-hydroxy-2-di-n-propylamino-tetralin (8-OHDPAT, 0.3 mg/kg) induces also an insomnia which, unlike Apo, is followed by a significant PS rebound. CLIP, again, antagonizes the 8-OHDPAT-induced insomnia. Finally, Bromocriptine (5 mg/kg), an agonist for both DA and 5-HT, induces first an insomnia (antagonized by CLIP), followed by a PS rebound; these effects persist in hypoX rats.
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PMID:Proopiomelanocortin (POMC)-derived peptides and sleep in the rat. Part 2--Aminergic regulatory processes. 196 3

The sleep-wake effects of the proopiomelanocortin (POMC)-derived peptides, i.c.v. injected, are reported. Adrenocorticotropic hormone (ACTH, 1 microgram) induces an awakening effect, while its two derivatives, desacetyl-alpha-MSH (des-alpha-MSH, 1ng) and corticotropin-like intermediate lobe peptide (CLIP, 10 ng), are respectively able to increase slow wave sleep (SWS) and paradoxical sleep (PS); the hypnogenic effect of CLIP is also observed in hypophysectomized rats. Furthermore, two hypothalamic factors known to be involved in the control of POMC derivatives were also injected; MSH inhibiting Factor (MIF) does not influence the vigilance states, while Corticotropin Releasing Factor (CRF, 1 microgram) increases the waking state. Finally, some preliminary results, obtained with a restraint stress and suggesting a possible interrelation between stress, sleep and POMC derivatives, are discussed.
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PMID:Proopiomelanocortin (POMC)-derived peptides and sleep in the rat. Part 1--Hypnogenic properties of ACTH derivatives. 198 27

The specific melanotropin (MSH) binding sites of rat lacrimal glands were characterized with respect to anatomic distribution, peptide specificity and selectivity, and coupling to a biological response. Tissue distribution of MSH binding sites was determined by autoradiography following in situ binding of a radiolabeled, biologically active preparation of a superpotent alpha-MSH analog, [125I]-[Nle4,D-Phe7]-alpha-MSH ([125I]-NDP-MSH). Intense, specific (i.e., alpha-MSH-displaceable) [125I]-NDP-MSH binding was observed throughout lacrimal acinar tissue, but not in ducts or stroma. In freshly isolated lacrimal acinar cells, specific binding of [125I]-NDP-MSH was maximal within 30 min and rapidly reversible, with a dissociation half-time of about 15 min. A number of melanotropins [alpha-MSH, [N,O-diacetyl-Ser1]-alpha-MSH, [des-acetyl-Ser1]-alpha-MSH, beta-MSH, ACTH(1-24) and ACTH(1-39)] were recognized by these binding sites, as assessed by their inhibition of [125I]-NDP-MSH binding; NDP-MSH was the most potent (IC50 = 1.3 x 10(-9) M). In contrast, other peptides, including ACTH(4-10) and the nonmelanotropic peptides VIP, substance P, somatostatin, and ACTH(18-39) (CLIP), had no effects on tracer binding. In isolated lacrimal acinar cells, alpha-MSH and NDP-MSH stimulated intracellular cyclic AMP accumulation. We conclude that lacrimal acinar cells express functional receptors recognizing melanotropins, suggesting that the lacrimal gland may be a target for physiological regulation by endogenous melanotropins.
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PMID:Characterization of functional melanotropin receptors in lacrimal glands of the rat. 216 77

After the recent demonstration of the facilitatory effect exerted by corticotropin-like intermediate lobe peptide (CLIP or adrenocorticotropic hormone (ACTH) 18-39) on paradoxical sleep in the rat (Chastrette and Cespuglio, 1985), we undertook the production of monoclonal antibodies against this peptide. Wistar rats were immunized against CLIP and their spleen cells fused with mouse myeloma cells. After recloning, 25 supernatants were found to give positive immunohistochemical reactions in the rat brain. In immunohistochemical tests performed by preabsorption, the 25 supernatants presented similar properties, i.e. recognized CLIP, ACTH (1-39) and ACTH (25-39), but not ACTH (1-24) and the C-terminal fragment (34-39). We assume that the epitope(s) recognized by the 25 supernatants is (are) located between the amino-acids Asn25 and Ala34 of the CLIP molecule. The immunoreactivity observed in the rat brain and hypophysis with this antibody was distributed with a pattern quite similar to that described for anti-ACTH antibodies. A main group of immunoreactive cell bodies was located in the mediobasal hypothalamus and a small group in the nucleus of the solitary tract. Immunoreactive fibres were distributed from the olfactory nucleus to the spinal cord and formed particularly rich networks in the hypothalamus and preoptic area. Among other locations, immunoreactive axons were also present in the brainstem centres involved in the control of the sleep-waking cycle, which is in accordance with the influence of CLIP on paradoxical sleep. Using Abercrombie's formula, the number of immunoreactive cells in the mediobasal hypothalamus was estimated at about 3000 neurons. We conclude that our monoclonal anti-CLIP antibody can be considered as a good marker of proopiomelanocortin neurons.
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PMID:A monoclonal antibody directed against CLIP (ACTH 18-39). Anatomical distribution of immunoreactivity in the rat brain and hypophysis with quantification of the hypothalamic cell group. 216 15

Because so-called 'carcinoid' tumour of the breast has proven to be a difficult entity to define, we studied in-situ carcinoma as there were reasons to believe that this might help clarify the complex problems involved. We studied a consecutive series of 30 cases of ductal carcinoma in-situ (DCIS) by light microscopy and silver impregnation methods and identified a relatively common endocrine variant of DCIS. This variant was studied by immunocytochemical and ultrastructural methods, using conventional DCIS as a control. Endocrine DCIS is identified by its organoid pattern, stromal 'inclusions', festooned structure and a distinctive type of polypoid invagination. It is argyrophilic and rich in neuron-specific enolase. Ultrastructurally it contains abundant dense core granules which are impregnated selectively by Grimelius' method. This tumour type frequently contains peptide hormones of the ACTH family. Three of seven cases contained cells reactive for ACTH and corticotropin-like intermediate lobe peptide CLIP or their precursor, pro-opiomelanocortin. A fourth tumour contained neurotensin, recently identified in a variety of endocrine tumours. Argyrophil invasive carcinomas are a much more heterogeneous group of tumours than argyrophil DCIS and only a minority have an endocrine structure comparable to that described here.
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PMID:A morphological and immunocytochemical study of a distinctive variant of ductal carcinoma in-situ of the breast. 1789 2

In the present study, a polyclonal antibody against pro-opiomelanocortin derivatives was characterized biochemically. Its immunoreactivity with structures of the arcuate nucleus and the median eminence was investigated by means of the immunogold method and compared with its reaction on adenohypophyseal cells with and without pre-adsorption with pro-opiomelanocortin derivatives. The antiserum detects ACTH and its fragments, in particular alpha-MSH, and beta-endorphin. In the adenohypophysis gold particles are exclusively located on small secretory granules situated in the periphery of branched cells. In the perikarya of the arcuate nucleus gold particles are observed on terminal vesicles abutting from the cis-face of the Golgi apparatus, on granules in its direct vicinity and on small dense core vesicles preferentially located in the cell periphery. Immunoreactive gold-labeled fiber profiles are found in a sub- or intra-ependymal position as well as in the nuclear neuropil proper. Here axodendritic and axosomatic synapses are observed. In both situations the gold particles are mostly restricted to the small dense core vesicles and do not decorate the synaptic vesicles. In the median eminence gold labeled fibers are detected in all layers. The labeled fibers can be closely apposed to tanycytic processes, without, however, forming special contact differentiations. In direction to the perivascular layer of the external zone the labeled profiles are more frequently arranged in groups intermingled with unlabeled fibers. The axons decorated with gold particles can be freely exposed to the perivascular space or are found as single processes in close vicinity to the capillary wall. Subsequent to preincubation of the native antiserum with ACTH1-39 and ACTH18-39 (= CLIP) neither adenohypophyseal cells nor perikarya and fibers in the arcuate nucleus nor axons in the median eminence are decorated with gold particles. Preincubation of the native antiserum with alpha-MSH or beta-endorphin does not change the immunoreaction with the small, peripherally situated granules in the branched adenohypophyseal cells. In neurons of the arcuate nucleus and in fibers of the median eminence, however, the immunoreaction is completely extinguished when the antibody is pre-incubated with alpha-MSH, whereas subsequent to preincubation with beta-endorphin only the amounts of labeled structures are reduced.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The bifunctional role of pro-opiomelanocortin derivatives in the mediobasal hypothalamus of the rat. 262 60


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