UNIPROT:P01178 - FACTA Search

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Query: UNIPROT:P01178 (oxytocin)
15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of TRH upon neurohypophyseal hormone release were studied in conscious rabbits. Intravenous infusion of 250 nm/kg TRH had no significant effect on either arginine vasopressin (AVP) or oxytocin (OT) release, but a 5-fold greater dose led to significant increases in plasma levels of both AVP and OT and behavioral arousal. Intraventricular injection of 3 nm TRH produced significant elevations of both plasma AVP and OT, with even greater effects on behavior than after iv infusion. The maximal hormone response to intraventricular injection was observed considerably earlier than that for iv injection and the response occurred after an almost 1000-fold lower dose of TRH. Neither artificial cerebrospinal fluid vehicle nor the inactive analogue D-tyrosine2 TRH (p-Glu-d-Tyr-Proamide) had any effect on neurohypophyseal hormone release or on behavior. MK-771 [L-N-(2-oxopiperidin-6-YL-carbonyl)-L-histidyl-L-thiazolidine-4-carboxamide], a TRH analog with enhanced central nervous system effects, had effects on AVP and OT release comparable to equimolar doses of TRH. TRH stimulates release of both AVP and OT after both intraventricular and iv injection, and these effects may be independent of behavioral activation.
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PMID:Thyrotropin-releasing hormone stimulates release of arginine vasopressin and oxytocin in vivo. 10 88

An enzyme which catalyzes the deamidation of thyroliberin (TRF; less than Glu-His-Pro-NH2) has been purified 110-fold from extracts of bovine anterior pituitary by ammonium sulfate fractionation, ion exchange chromatography on DEAE-cellulose, and gel filtration. This enzyme of 76,000 molecular weight (as estimated by gel filtration) exhibits maximal activity at neutral pH (optimum pH 7.4 to 7.6) in buffers of high ionic strength supplemented with thiol-protecting agents. As indicated by the strong inhibition of the enzymatic activity by N-ethylmaleimide and Hg2+, as well as by the extreme sensitivity toward diisopropyl fluorophosphate, -SH, and -OH residues apparently represent essential functional groups of the enzyme. The stereospecific deamidation of TRF (Km = 4.1 . 10(-4) M) is inhibited competitively by TRF analogues which contain proline or by the proline containing biologically active peptides luliberin (LH-RF), oxytocin, vasopressin, angiotensin II, and Substance P. TRF analogues without proline or peptide amides without proline are ineffective. This enzyme cleaves the appropriate Pro-X bonds in luliberin, angiotensin II, pyroGlu-His-Pro-Gly-NH2, and the collagenase substrate Z-Gly-Pro-Leu-Gly-Pro. Thus, it may be characterized as a post-proline-cleaving enzyme.
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PMID:Characterization of "thyroliberin-deamidating enzyme" as a post-proline-cleaving enzyme. Partial purification and enzyme-chemical analysis of the enzyme from anterior pituitary tissue. 11 64

A continuous cell line was previously obtained by Simian Virus (SV) 40 transformation of primary cultures of dissociated mouse fetal hypothalami. One clone from this cell line has been previously shown to possess some of the ultrastructural features, immunological properties and synthesizing capacities of magnocellular hypothalamic neurons which secrete vasopressin and neurophysins. The present paper reports on the morphological characterization of 14 other clones or subclones of the original cell line, using the following criteria: phase contrast microscopy, electron microscopy, Gomori's aldehyde fuchsin staining, cytochemical detection of beta-glucuronidase, immunochemical staining with antisera against bovine neurophysin I, bovine neurophysin II, lys-vasopressin, oxytocin, LH-RH and TRH. The results allowed the conclusion that the clones as well as the subclones can be distributed into two groups: 1) neurosecretory neurons which all possess several of the ultrastructural and cytochemical features of the neurophysin-vasopressin synthesizing clone, and 2) primitive nerve cells which are devoid of such features but display numerous bundles of filaments. In addition some clones were found to display intermediate features between groups 1 and 2. A similar diversity was observed within clones of the original strain and subclones of a neurosecretory clone. It is suggested that the primitive clones could represent precursors of the neurosecretory clones.
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PMID:Ultrastructural and cytochemical features of SV 40 transformed hypothalamic cell lines. 18 90

The rate of hydrolysis of several aminoacyl-4-nitroanilides by rat hypothalamic arylamidases was investigated. The activity of these enzymes which were mainly found in the 105 000 times g supernatant fraction of homogenates of the hypothalamus and other parts of the brain was shown to depend upon the presence of metal ions and free thiol groups, and to be inhibited by puromycin. As previous investigations had shown that Cys-NA is an appropiate substrate for measuring hormone effects on hypothalamic arylamidases, L-cystine arylamidase and its interaction with various peptide hormones were examined in detail. It could conclusively be shown that this enzyme interacts particularly with oligopeptides. Its activity was competitively inhibited by TRF, oxytocin, lysine vasopressin, and LH-RH. It was also shown that the biological activity of LH-RH and its inhibitory effect on the hydrolysis of L-cystine-bis-p-nitroanilide decreased when it was incubated for various periods of time with the 105 000 times g supernatant of rat hypothalumus homogenate.
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PMID:Inactivation of luteinizing hormone releasing hormone by rat hypothalamic L-cystine arylamidase. 80 61

The reaction products of plasma enzyme degradation of TRH were identified by thin layer chromatography. The enzyme in normal rat plasma yields proline and pGlu-His as major reaction products. High concentrations of proline decrease peptide cleavage, resulting in greater amounts of acid TRH. The apparent Km of the enzyme is 4.1 X 10(-6) M. LHRH and neurotensin are competitive inhibitors with Ki of 5 X 10(-6) M and 1.5 X 10(-5) M, respectively. Somatostatin, MIF, oxytocin, arg-vasopressin, arg-vasotocin, neurophysin II and glucagon do not compete; and pGlu-His-Pro-OH, Glu-His-Pro-OH, pGlu-His, His-Pro-NH2, and Pro-NH2 do not affect enzyme activity. These data suggest that the substrated requires pGlu and a terminal or internal amide to complex with the enzyme. The enzyme is markedly inhibited by Cu++, Bal, benzamadine, p-(chloromercuri)-benzoic acid, moderately affected by EDTA and puromycin, and unaffected by mercaptoethanol. TSH does not affect enzyme activity while LH inhibits it moderately at high concentrations (300-600 pg/ml).
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PMID:Characteristics of the plasma TRH-degrading enzyme. 81 19

Hybridization histochemistry has bridged molecular biology and neuroanatomy to provide nearly dynamic views of gene expression in the brain--perhaps especially in the hypothalamus. These snapshots of transcript levels with precise anatomical localization have revealed new insights into gene regulation in the hypothalamus under specific conditions. Magnocellular neurons in the paraventricular and supraoptic nuclei produce vasopressin and oxytocin. Transcript levels for these hormones are affected by hyperosmolality, as are those for many other neuropeptides. Patterns of gene expression in the magnocellular neurons in these nuclei during development and under different physiological conditions have been studied less extensively. The parvocellular neurons of the paraventricular nucleus produce corticotropin-releasing factor and thyrotropin-releasing hormone. Expression of the corticotropin-releasing factor gene is regulated by glucocorticoids. Physiological stresses, which activate the hypothalamo-pituitary-adrenal axis, also affect gene expression in the parvocellular paraventricular nucleus. Thyrotropin-releasing hormone is synthesized in a different set of parvocellular neurons in the paraventricular nucleus and in other neurons of the hypothalamus. Expression of the thyrotropin-releasing hormone gene is regulated by thyroid hormone. The suprachiasmatic nucleus contains neurons that produce vasopressin or vasoactive intestinal polypeptide in a circadian rhythm. Future studies using combinations of classical neuroanatomical techniques, hybridization histochemistry and immunohistochemistry will further our understanding of hypothalamic responses to various stimuli.
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PMID:Regulation of gene expression in the hypothalamus: hybridization histochemical studies. 142 21

The synthesis and release of PRL are regulated by a variety of factors that originate in the hypothalamus, peripheral tissues, or posterior pituitary (PP). We recently reported that coculture of anterior pituitary (AP) and PP cells induced an increase in both PRL cell content and the responsiveness of lactotrophs to TRH. The aim of the present study was to determine whether the augmented response to TRH is due to increased lactotroph sensitivity to this particular secretagogue or to enhancement of the releasable pool of PRL. Cells obtained from anterior pituitaries of adult male rats were plated either alone or together with PP cells at the same total density. Cells cultures were maintained in serum-free medium for 4 days and then incubated for 20 min with the designated substances. Angiotensin-II and TRH evoked a significantly larger release of PRL in AP + PP cocultures than in AP cells cultured alone; the greatest difference between the culture types was observed at the highest concentrations of both secretagogues. The stimulation of PRL release by KCl, the calcium ionophore A23187, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate was higher in the presence of PP cells than in cultures of AP cells alone, although the magnitude of this effect was lower than that seen with PRL secretagogues. The concomitant application of A23187 and 12-O-tetradecanoylphorbol-13-acetate resulted in an increased response in both types of culture and a greater relative effect of PP cells on the evoked PRL release. In contrast to other secretagogues, oxytocin (OT) elicited a smaller response in AP + PP cocultures than in AP cultures. OT was present in significant amounts in medium from cocultures, apparently after being released from the severed neuronal terminals. When AP cultures were pretreated for 4 days with comparable concentrations of OT, the acute OT-evoked PRL release was greatly diminished. These findings suggest that coculture with PP cells increases the releasable pool of PRL in lactotrophs. The stored PRL is accessible for release by secretagogues known to act via the Ca2+ second messenger system, involving both Ca2+/calmodulin and protein kinase-C pathways. The diminished response of cocultures to OT is probably due to desensitization of lactotrophs by the residual amounts of this peptide present in the disrupted nerve endings.
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PMID:Effects of coculture of anterior and posterior pituitary cells on the responsiveness of lactotrophs to different secretagogues. 193 84

The central action of peptides to influence GI motility in experimental animals is summarized in Table 1. TRH stimulates gastric, intestinal, and colonic contractility in rats and in several experimental species. A number of peptides including calcitonin, CGRP, neurotensin, NPY, and mu opioid peptides act centrally to induce a fasted MMC pattern of intestinal motility in fed animals while GRF and substance P shorten its duration. The dorsal vagal complex is site of action for TRH-, bombesin-, and somatostatin-induced stimulation of gastric contractility, and for CCK-, oxytocin- and substance P-induced decrease in gastric contractions or intraluminal pressure. The mechanisms through which TRH, bombesin, calcitonin, neurotensin, CCK, and oxytocin alter GI motility are vagally mediated. An involvement of central peptidergic neurons in the regulation of gut motility has recently been demonstrated in Aplysia, indicating that such regulatory mechanisms are important in the phylogenesis. Alterations of the pattern of GI motor activity are associated with functional changes in transit. TRH is so far the only centrally acting peptide stimulating simultaneously gastric, intestinal, and colonic transit in various animals species. Opioid peptides acting on mu receptor subtypes in the brain exert the opposite effect and inhibit concomitantly gastric, intestinal, and colonic transit. Bombesin and CRF were found to act centrally to inhibit gastric and intestinal transit and to stimulate colonic transit in the rat. The antitransit effect of calcitonin and CGRP is limited to the stomach and small intestine. The delay in GI transit is associated with reduced GI contractility for most of the peptides except central bombesin that increases GI motility. Nothing is known about brain sites through which these peptides act to alter gastric emptying and colonic transit. Regarding brain sites influencing intestinal transit, TRH-induced stimulation of intestinal transit in the rat is localized in the lateral and medial hypothalamus and medial septum. The periaqueductal gray matter is a responsive site for mu receptor agonist- and neurotensin-induced inhibition of intestinal transit. The neural pathways from the brain to the gut whereby these peptides express their stimulatory or inhibitory effects on GI transit is vagal dependent with the exception of calcitonin. It is not known whether the vagally mediated inhibition of GI transit by these peptides results from a decrease activity of vagal preganglionic fibers synapsing with excitatory myenteric neurons or an activation of vagal preganglionic neurons synapsing with inhibitory myenteric neurons. The lack of specific antagonists for these peptides has hampered the assessment of their physiological role.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Central nervous system action of peptides to influence gastrointestinal motor function. 210 14

The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 micrograms/rat stimulated a moderate PRL release in the morning and lower doses (5 and 10 micrograms) were without effect. Vasopressin was most effective at a dose of 5 micrograms/rat in stimulating PRL release, while consecutive injections of higher doses (10 and 20 micrograms) were less effective. In contrast, TRH, ranging from 1 to 8 micrograms/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT [( 1-(beta-mercapto-beta, beta-cyclopentamethylene propanoic acid), 2-(O-methyl)tyrosine, 8-ornithine]-vasotocin) and d (CH2)5Tyr(Me)AVP ([1-(beta-mercapto-beta, beta-cyclo-pentamethylene propionic acid), 2-(O-methyl)tyrosine, 8-arginine]-vasopressin), were given hourly between 1300 to 1800 h and blood samples were obtained hourly from 1100 to 1900 h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective. When OT or AVP were administered together with their specific antagonists, the inhibitory effects of either hormone on PRL surge were reversed. Thus it is concluded that both OT and AVP assume a non-specific stress-like effect on PRL release, in which basal secretion is stimulated and surge secretion is inhibited.
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PMID:Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge. 212 15

Cold exposure increases blood levels of TSH and thyroid hormones by stimulating the secretion of TRH from the median eminence. Thyroid hormones reduce TRH release and cellular levels of TRH mRNA. Using quantitative in situ hybridization to measure changes in cellular levels of various neuropeptide mRNAs, the present studies demonstrate that cold exposure also increases cellular levels of TRH mRNA in neurons of the paraventricular nucleus (PVN), supporting the concept that TRH mRNA levels are reflective of TRH secretion in these neurons. The effect of cold appeared to be specific for TRH expression in the PVN, because cold exposure did not influence cellular levels of TRH in the reticular thalamic nucleus or beta-actin and oxytocin mRNAs in the PVN. Cellular levels of mRNA encoding CRH were elevated by cold exposure. This latter observation is predictable based on the cold-induced activation of the hypothalamic-pituitary-adrenal axis. There was a 24-h rhythm and a time of day difference in the effect of cold on TRH mRNA levels in the PVN. Time of day differences in the effect of cold on CRH mRNA levels were not apparent. Cold exposure appeared to elevate TRH mRNA levels in all neurons of the PVN, indicating that the neurally mediated effect of cold on TRH expression can override the inhibitory effects of circulating T3 within the same neuronal population.
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PMID:Cold exposure elevates cellular levels of messenger ribonucleic acid encoding thyrotropin-releasing hormone in paraventricular nucleus despite elevated levels of thyroid hormones. 212 45

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