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)

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

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

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

Plasma ACTH and cortisol concentrations are frequently elevated in patients in intensive care units (ICU). To examine the functional integrity of the hypothalamic-pituitary-adrenal axis during critical illness, we evaluated prospectively 53 ICU patients in a general medical ICU. Thirty-one patients and 7 normal controls underwent an overnight dexamethasone suppression test (3 mg dexamethasone, orally, at 2300 h). Plasma ACTH and serum cortisol were measured at 0900 h. In a separate experiment, 22 patients and 7 control subjects underwent a CRH stimulation test [100 micrograms human (h) CRH, iv]. ACTH and cortisol concentrations were determined from -15 to 120 min. Compared to normal controls, plasma ACTH and serum cortisol concentrations were not fully suppressible by dexamethasone [mean +/- SEM: plasma ACTH, 21 +/- 4 vs. 3 +/- 0.5 pg/mL (4.7 +/- 0.9 vs. 0.7 +/- 0.1 pmol/L); serum cortisol, 13.9 +/- 1.9 vs. 1.5 +/- 0.3 micrograms/dL (390 +/- 50 vs. 40 +/- 10 nmol/L); P = 0.0001], demonstrating an altered glucocorticoid feedback in the ICU patients. Patients undergoing hCRH stimulation had clearly elevated mean baseline plasma ACTH and serum cortisol concentrations [ACTH, 78 +/- 20 pg/mL vs. 15 +/- 3 in controls (17.2 +/- 4.4 vs. 3.4 +/- 0.7 pmol/L; P = 0.007); cortisol, 36.8 +/- 3.4 micrograms/dL vs. 9.6 +/- 1.2 (1020 +/- 80 vs. 260 +/- 30 nmol/L; P = 0.0001)]. Despite elevated baseline glucocorticoid concentrations, stimulation with hCRH resulted in significantly higher peak plasma ACTH concentrations 15 min after hCRH than in controls [134 +/- 31 vs. 48 +/- 9 pg/mL (29.5 +/- 6.8 vs. 10.6 +/- 2.0 pmol/L); P < 0.05]. Serum cortisol concentrations in ICU patients were significantly elevated throughout the test period (P = 0.0001) and rose to a peak of 43.9 +/- 3.5 micrograms/dL compared to 18.2 +/- 2.0 micrograms/dL in controls (1210 +/- 70 vs. 500 +/- 60 nmol/L). We conclude that ICU patients have a markedly altered responsiveness of their pituitary corticotroph to suppression with dexamethasone and stimulation with hCRH. These findings may be explained by altered pituitary glucocorticoid feedback and/or hypersecretion of peptides with CRH-like activity (vasopressin and cytokines) during critical illness.
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PMID:The hypothalamic-pituitary-adrenal axis in critical illness: response to dexamethasone and corticotropin-releasing hormone. 839 81