Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Coexisting with oxytocin or vasopressin in the cell bodies and nerve terminals of the hypothalamic-neurohypophysial system are smaller amounts of other peptides. For a number of these "copeptides" there is strong evidence of corelease with the major magnocellular hormones. Guided by the location of their specific receptors we have studied the effects of three copeptides, dynorphin, cholecystokinin (CCK), and corticotropin releasing hormone (CRH), on the secretion of oxytocin and vasopressin from isolated rat neural lobe or neurointermediate lobe preparations in vitro. 2. Dynorphin is coreleased with vasopressin from neural lobe nerve terminals and acts on neural lobe kappa-opiate receptors to inhibit the electrically stimulated secretion of oxytocin. Naloxone augments oxytocin release from the neural lobe in a manner directly proportional to the amount of vasopressin (and presumably dynorphin) released. 3. Cholecystokinin, coreleased with oxytocin by neural lobe terminals, has been shown to have high-affinity receptors located in the NL and to stimulate secretion of both oxytocin and vasopressin. CCK's secretagogue effect was independent of electrical stimulation and extracellular Ca2+ and was blocked by an inhibitor of protein kinase C. 4. CRH, coreleased with OT from the neural lobe, has receptors in the intermediate lobe of the pituitary, but not in the neural lobe itself. CRH stimulates the secretion of oxytocin and vasopressin from combined neurointermediate lobes but not from isolated neural lobes. Intermediate lobe peptides, alpha and gamma melanocyte stimulating hormone, induced secretion of oxytocin and vasopressin from isolated neural lobes. Their effect was, like that of CCK, independent of electrical stimulation and extracellular Ca2+ and blocked by an inhibitor of protein kinase C. 5. Among the CRH-producing parvocellular neurons of the paraventricular nucleus, in the normal rat, approximately half also produce and store vasopressin. After removal of glucocorticoid influence by adrenalectomy, virtually all of the CRH neurons contain vasopressin. 6. The two subtypes of CRH neurosecretory cells found in the normal rat possess different topographical distributions in the paraventricular nucleus, suggesting the possibility of differential innervation. Stress selectively activates the vasopressin containing subpopulation of CRH neurons, indicating that there are separate channels of regulatory input controlling the two components of the parvocellular CRH neurosecretory system.
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PMID:Coexisting peptides in hypothalamic neuroendocrine systems: some functional implications. 257 30

A 51-yr-old male patient with Cushing's syndrome due to huge nodular adrenocortical hyperplasia is described. Urinary 17-OHCS was not suppressed by a high dose of (8 mg) dexamethasone and showed rather a tendency to paradoxical response. There was no response to metyrapone. Plasma cortisol showed a hyperresponse to insulin-induced hypoglycemia and a rapid response to corticotropin releasing hormone-lysine vasopressin (CRH-LVP) administration without an obvious ACTH response. Plasma cortisol responded to synthetic ACTH. Urinary 17-OHCS did not show parallel changes with plasma cortisol. These results and computerized tomography data suggested huge multiple nodular adrenocortical hyperplasia, which was confirmed later by surgery. The left and right adrenal glands weighed 105 and 45 g, respectively. Hyper-reaction of the adrenal gland to a small change in plasma ACTH or "unknown factors" may cause not only the discrepancy between cortisol and ACTH response but also the development of autonomous nodules in the adrenal gland.
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PMID:Cushing's syndrome due to huge nodular adrenocortical hyperplasia with fluctuation of urinary 17-OHCS excretion. 262 Jun 63

The data highlighted here suggest that the CRH effects of vasopressin and oxytocin are mediated by one and the same hypophysial receptor which has unique pharmacological specificity. The nomenclature for this receptor type is not established; both V3(53) and V1 beta 39 have been proposed. The former proposal is logical if the pharmacology of ligand recognition is emphasized, whereas the latter designation takes into account that transmembrane signalling from V1 receptors occurs via coupling proteins Go and Gi but not Gs. Such issues are best resolved after cDNA cloning of the genes for the receptors: in the meanwhile the working definition V3 seems more convenient. Several studies show that pituitary V3 receptors are regulated by the concentration of vasopressin in hypophysial portal blood and the amount of glucocorticoid hormones in the circulation (see Ref. 9 for review). Work in this area should clarify further the intracellular mechanism of the CRH action of vasopressin, as well as the factors that determine the responsiveness of corticotrophs to various secretagogues. Most recently, it has been shown that vasopressin is a potent thyrotropin-releasing hormone. This finding extends further the growing concept that there is considerable "cross-talk" between the classical neuroendocrine axes. These were previously thought to be separated by the hypothalamic organization of "final common pathways" of neuroendocrine motoneurons in the hypothalamus, each producing a unique neurohormone to regulate a single type of adenohypophysial cell. It seems that the days of the validity of this hypothesis are numbered, and an important task will be to determine the possible physiological significance of the "cross-talk" within the hypothalamo-pituitary unit in the regulation adrenocortical function.
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PMID:Receptors mediating the CRH effects of vasopressin and oxytocin. 283 75

There is evidence that the peptides derived from proopiomelanocortin as well as the neurohypophyseal hormones exert important and substantial effects on brain functions after intracerebroventricular and peripheral administration. This led us to study the effects of intravenous hCRH on brain functions in humans using electroencephalographic techniques. In our experience the event-related potentials (e.g. auditory evoked potentials) provide a sensitive and accurate assay systems to study such effects of peptides. Male volunteers were tested in a dichotic listening paradigm, providing electrophysiological measures of selective attention. Human CRH (50 micrograms/hr i.v.) augmented selective attention as indicated by an increased difference between evoked potential waveforms to attended and to unattended stimuli. The opposite results, a decrease in selective attention, was observed after treatment with the behavioral active fragment of adrenocorticotropin, ACTH 4-10. In comparison to ACTH 4-10, lysine-vasopressin, and cortisol, CRH displayed a unique pattern of influences on event related potentials. From these results we conclude that CRH can affect brain function in man and does so by a direct action on the brain and not only by stimulating the release of other behavioral active hormones.
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PMID:Effects of corticotropin releasing hormone on human brain function: an analysis based on auditory evoked potentials. 283 98

Human placenta contains the POMC-derived peptides ACTH, alpha MSH, and beta-endorphin, and CRH. High concentrations of immunoreactive (IR) CRH have been recently demonstrated in maternal plasma during pregnancy. To determine if the human placenta secretes CRH and POMC-derived peptides, we developed an in vitro human placental fragment perifusion system. The perifused tissue released IR-CRH and POMC-derived peptides at a constant rate for at least 5 h. The mean IR-CRH concentration in the effluent (under basal conditions) was 158 +/- 26 (+/- SD) pg (34.5 +/- 5.8 fmol)/5-min fraction.g tissue. IR-alpha MSH, IR-beta-endorphin, and IR-ACTH were also released into the perifusion medium; the mean concentration of alpha MSH released was 24.6 +/- 8 pg (14.8 +/- 4.8 fmol)/fraction.g, that of ACTH was 2.9 +/- 1.9 pg (0.65 +/- 0.43 fmol)/fraction.g, and that of beta-endorphin was 12.9 +/- 6 pg (3.8 +/- 1.7 fmol)/fraction.g. We examined the effects of human CRH, oxytocin, vasopressin, and dexamethasone on placental POMC peptide secretion. Five-minute pulses of 10(-8) or 10(-6) mol/L human CRH or oxytocin produced an immediate and dose-dependent increase in all POMC peptides in the effluent. A 5-min pulse of 10(-8) or 10(-6) mol/L vasopressin had no effect. A continuous 4-h exposure to 10(-6) mol/L dexamethasone had no effect on either basal IR-CRH or POMC-derived peptide or their KCl-induced release. In conclusion, we found that 1) human placenta releases IR-CRH and POMC-derived peptides in vitro; this phenomenon seems to be independent of glucocorticoid control; 2) placental CRH may have a paracrine effect on placental POMC peptide release in addition to its possible action on maternal pituitary hormone release; and 3) oxytocin, but not vasopressin, stimulates placental POMC peptide release.
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PMID:Corticotropin-releasing hormone and oxytocin stimulate the release of placental proopiomelanocortin peptides. 283 12

Exogenously administered vasopressin (VP) augments ACTH secretion stimulated by CRH. This study was performed to elucidate the role of endogenous VP in potentiating CRH-induced ACTH secretion in man. Synthetic human CRH (100 micrograms) was injected iv into seven normal men after they had been water loaded (20 mL/kg; 60 and 30 min before CRH injection; WL-CRH test) and water deprived (water restriction for 18 h before CRH injection; WD-CRH test). Blood samples were obtained before and 5, 15, 30, 60, 90, and 120 min after CRH injection at 0900 h for determination of plasma ACTH, cortisol, arginine vasopressin (AVP), CRH, and catecholamine levels and osmolality. Urine was obtained immediately before and 120 min after CRH injection for determination of osmolality. The mean plasma AVP levels were significantly higher during the WD-CRH test [1.8 +/- 0.4 (+/- SE) to 1.9 +/- 0.4 pmol/L] than during the WL-CRH test (0.6 +/- 0.1 to 0.9 +/- 0.1 pmol/L). The mean plasma ACTH and cortisol levels rose significantly from basal (4.5 +/- 0.6 pmol/L and 320 +/- 20 nmol/L, respectively) to peak values of 14.0 +/- 2.1 pmol/L at 30 min and 700 +/- 50 nmol/L at 60 min, respectively, during the WD-CRH test. During the WL-CRH test, mean basal plasma ACTH and cortisol levels were 3.5 +/- 0.7 pmol/L and 420 +/- 50 nmol/L, respectively, and reached peak values of 7.7 +/- 1.1 pmol/L at 60 min and 550 +/- 40 nmol/L at 30 min, respectively. Both the mean peak levels and integrated ACTH and cortisol responses were significantly higher during the WD-CRH than during the WL-CRH test. There was no significant difference between the plasma CRH and catecholamine concentrations in both tests. These results suggest that endogenous AVP potentiates CRH-stimulated ACTH secretion and, thus, plays a physiologically significant role in regulating CRH-stimulated ACTH and cortisol secretion in man.
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PMID:Role of endogenous arginine vasopressin in potentiating corticotropin-releasing hormone-stimulated corticotropin secretion in man. 283 68

Two groups of six healthy young males participated in separate experiments to examine the physiological role of endogenous vasopressin in h-CRH-induced (100 micrograms iv) ACTH release: a) after drinking of 3500 ml of water; b) after thirsting for 23 h; c) after 0.9% saline infusion, and d) after 5.0% saline infusion (0.06 ml/kg per min for 120 min). AVP levels were markedly elevated (4 ng/l) after thirsting and 5% saline infusion when compared with water loading or infusion of physiological saline. Although basal and h-CRH-stimulated ACTH and cortisol levels tended to be higher during hypertonic saline infusion and dehydration, no significant difference was observed between states of high or low endogenous AVP levels. These results are not in accordance with previous studies using ovine CRH, which might be due to its longer half-time or the timing of the changes in AVP plasma levels in relation to the CRH injection. Our data suggest that the osmotic modulation performed in this study results in AVP concentrations in the adenohypophysis, which are in the threshold range for influencing ACTH release induced by exogenous h-CRH.
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PMID:Effects of osmotically stimulated endogenous vasopressin on basal and CRH-stimulated ACTH release in man. 283 80

A human plasma CRH-binding protein (CRH-BP) was identified and characterized by chemical cross-linking of 125I-Tyr-hCRH to human plasma using disuccinimidyl suberate. The apparent mol wt of the cross-linked complex determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography was approximately 43,000. The mol wt was slightly lower in the nonreduced state, suggesting the presence of intramolecular disulfide bonds. Subtracting the mol wt of 125I-Tyr-CRH, the BP appeared to have a mol wt of approximately 38,000. Binding was specific since the appearance of the 43,000 dalton band was not affected by unlabeled ACTH, vasopressin, serum albumin, or gamma-globulin, but was inhibited by unlabeled hCRH dose dependently. Pretreatment of plasma with 0.1 mol/L HCl, 0.01 mol/L NaOH, 10 mmol/L dithiothreitol, or trypsin before cross-linking abolished its ability to bind 125I-Tyr-hCRH. Rat, rabbit, or goat plasma or human cerebrospinal fluid did not bind 125I-Tyr-CRH. It is unlikely that CRH-BP is a CRH receptor, because the estimated mol wt of the CRH-BP is smaller than the reported size of CRH receptors, and the CRH-BP did not bind to ovine CRH. The binding of 125I-Tyr-CRH to CRH-BP decreased in the third trimester of pregnancy, when plasma CRH levels were markedly elevated. However, after dissociating endogenous CRH from the CRH-BP, the binding was almost the same as in nonpregnant subjects. In addition, CRH-BP inhibited CRH-induced ACTH secretion from cultured rat anterior pituitary cells. We conclude that most of the increased plasma CRH found in pregnant women is bound to CRH-BP, and so is inactive, therefore plasma ACTH levels do not increase to above the normal range.
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PMID:Characterization of corticotropin-releasing hormone binding protein in human plasma by chemical cross-linking and its binding during pregnancy. 284 56

The transfer of information by chemical signals during complex biological processes can, with increasing frequency, be described in terms of interacting signal pairs. External signalling is rarely monolithic; rather, signal pairs are utilized in processes such as hormone secretion, neurotransmission, cell growth and differentiation. The dualism of external signalling often results in the occurrence of synergy. One signal appears to turn the cell on or off, and its synergistic partner increases cell responsiveness, providing gain control of the cellular response. ACTH release provoked by certain stressors arises from a synergistic interaction between two hypothalamic hormones: corticotropin releasing hormone (CRH) and a modulator such as vasopressin (AVP). The pituitary ACTH cell has been used to unravel the intracellular messenger equivalents of an external signal interaction that generates synergy. Research emphasizes the single cell approach. Direct measurements of intracellular free Ca2+ were performed using the Ca2+-sensitive fluorescent probe fura-2/AM and instrumentation for digital image processing. A reverse haemolytic plaque assay was used to measure cumulative ACTH release from single pituitary cells in culture. What is the physiological role of intracellular Ca2+ as a messenger? What are the feedforward and feedback relationships between major second messengers [cyclic AMP, diacylglycerol (DAG), inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)] and intracellular Ca2+? That is, how are individual messenger circuits "wired' within ACTH cells. Intracellular Ca2+ may act as a common signal into which interacting second messenger signals [cyclic AMP, Ins(1,4,5)P3, DAG] are transduced and integrated to govern ACTH release. A novel circuit of messenger pathways linked by Ca2+ is proposed as the intracellular basis for the synergistic interaction of CRH- and AVP-regulated ACTH release.
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PMID:A complex mechanism of facilitation in pituitary ACTH cells: recent single-cell studies. 285 Mar 35

CRH is a 41 amino acid peptide first isolated from ovine and subsequently from rat and human hypothalami. We have conducted a series of clinical studies with oCRH and hCRH in volunteers and patients with various disorders of hypothalamic-pituitary-adrenal function. In volunteers, it was demonstrated that hCRH administration produced ACTH and cortisol responses which closely mimic naturalistically occurring secretory episodes. This data, as well as the demonstration that pulsatile hCRH can reestablish normal ACTH and cortisol secretion in patients with hypothalamic CRH deficiency, strongly argue that CRH is of physiological relevance to the human pituitary-adrenal axis. However, since the ACTH response to an insulin tolerance test is greater than the maximal ACTH response to CRH, other factors such as vasopressin may be relevant to stress-induced ACTH secretion in man. Following the demonstration that CRH seems to be of physiological relevance to human subjects, a CRH stimulation test was developed based on pharmacokinetic and dose response studies with oCRH and hCRH. Based on these data, which revealed that oCRH functions as a long-acting analogue of hCRH, and the demonstration that hormonal responses to CRH are greatest in the evening, patient groups with abnormalities of the hypothalamic-pituitary-adrenal axis were tested with intravenous oCRH with a dose of 1 micrograms/kg given at 2000 hours. This CRH stimulation test has proved helpful in clarifying the pathophysiology of hypercortisolism in a variety of psychiatric disorders characterized by this endocrine abnormality. Thus, blunted ACTH responses in hypercortisolemic patients with depression, anorexia nervosa, and panic anxiety disorder indicate normality of the pituitary corticotroph in these patient subgroups. These data, along with the finding that a continuous infusion of CRH to normal volunteers, reproduces the pattern and magnitude of hypercortisolism in depression and anorexia nervosa, suggest that the hypercortisolism in these disorders represents a defect at or above the hypothalamus resulting in the hypersecretion of CRH. This hypothesis is particularly intriguing in light of the demonstration that CRH administration to experimental animals produces many of the physiological and behavioral responses classically associated with depression and anorexia nervosa, including hypercortisolism, hypothalamic hypogonadism, and decreases in libido and appetite. The CRH stimulation test has also helped to resolve one of the oldest endocrinological dilemmas, namely whether the hypercortisolism of depression and Cushing's disease share a common or dissimilar pathophysiological basis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Corticotropin releasing hormone: relevance to normal physiology and to the pathophysiology and differential diagnosis of hypercortisolism and adrenal insufficiency. 303 86


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