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)

A 44-yr-old man with hypocortisolism was shown to have an undetectable basal plasma ACTH level and absent or subnormal ACTH and beta-lipotropin responses to provocative testing with insulin, vasopressin, and CRH. Endocrine function after glucocorticoid replacement was otherwise normal, thus establishing the diagnosis of isolated ACTH deficiency. This patient's serum was tested immunohistochemically for the presence of an antipituitary antibody by indirect immunofluorescence of rat pituitary tissue. Positive immunostaining was observed in stellate-shaped cells in the anterior and intermediate lobes. Immunopositive cells were shown by immunoelectron microscopy to have ultrastructural characteristics of corticotrophs. Immunoreactivity was concentrated in secretory granules 120-170 nm in diameter. In a double immunolabeling procedure, staining by the patient's serum was shown to colocalize with rabbit antiserum to ACTH, but not with antisera to PRL, GH, beta TSH, or beta LH. Immunoabsorption of the patient's serum with ACTH-(1-24), ACTH-(1-39), gamma MSH, corticotropin-like intermediate lobe peptide, beta-endorphin, or beta-lipotropin failed to diminish immunolabeling in the pituitary. We conclude that the antipituitary antibody in this patient's serum shows immunohistochemical specificity for a rat corticotroph antigen located in secretory granules that is neither ACTH nor any of the proopiomelanocortin (POMC)-derived peptides tested. The autoantigen could be a cell-specific granular factor involved in the posttranslational processing of POMC or secretion of ACTH. We postulate that an autoimmune process may account for this patient's disease, and that his antipituitary antibody could play a pathogenic role by either inhibiting a POMC-processing enzyme or initiating an antibody-dependent cell-mediated cytotoxicity reaction, resulting in the selective destruction of corticotrophs.
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PMID:Isolated adrenocorticotropin deficiency associated with an autoantibody to a corticotroph antigen that is not adrenocorticotropin or other proopiomelanocortin-derived peptides. 215 84

Ten patients with secondary hypoadrenalism have been tested with corticotropin releasing hormone (CRH) and lysine-vasopressin (LVP). One patient had isolated ACTH deficiency; 9 had deficiency of other pituitary hormones attributable to a primary pituitary disease in 3 and to an hypothalamic disorder in 6. After CRH administration, a definite increase in plasma ACTH was observed in all 6 patients with hypothalamic disorder. No response was elicited in the 3 patients with pituitary disease and in the patient with isolated ACTH deficiency. In the responsive patients. ACTH showed a delayed and prolonged pattern of response. Lysine-vasopressin administration produced an increase in plasma ACTH in 4 of the 6 hypothalamic patients and no response in those with pituitary disease and in the patient with isolated ACTH deficiency. These findings suggest that CRH represents a reliable test in differentiating hypothalamic from pituitary adrenal failure; LVP appeared a less sensitive diagnostic test.
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PMID:CRH and lysine-vasopressin stimulation tests in the diagnosis of hypoadrenalism secondary to hypothalamic or pituitary disorders. 216 50

To examine the functioning of the hypothalamo-pituitary-adrenocortical axis in secondary adrenocortical insufficiency, we administered 100 micrograms synthetic human CRH, iv, plus 10 U lysine-8-vasopressin (LVP), im, three times daily for 3 consecutive days. The changes in plasma ACTH and cortisol levels during the administration and the response to an insulin tolerance test (ITT) conducted before and after the administration were determined. In three patients with isolated ACTH deficiency, basal plasma ACTH and cortisol levels were undetectablly low, and there was no response noted in the ITT or during CRH-LVP administration throughout the observation period. In four patients with adrenocortical insufficiency who had undergone successful transsphenoidal microadenomectomy for Cushing's disease and in six patients who had undergone curative unilateral adrenalectomy for Cushing's syndrome, basal plasma ACTH levels were low, but responded considerably to both stimulation tests. Along with the 3 days of CRH-LVP stimulation, however, neither the peak nor the time-integrated ACTH response was significantly enhanced, because of the variability of the responses among the patients. Compared with the ACTH response on the last day of CRH-LVP stimulation, the subsequent ITT tended to induce a lower ACTH response in the post-Cushing's disease patients and a higher response in the post-Cushing's syndrome patients. Regarding the plasma cortisol levels, the basal, peak, and integrated responses tended to increase daily during CRH-LVP administration. Conversely, the ITT after repetitive CRH-LVP administration induced a higher cortisol response than the test before CRH-LVP administration in the post-Cushing's disease patients. No serious complications were noted in any of the patients during or after the treatment. The present findings indicate that 1) repetitive administration of CRH in combination with LVP is a safe and valuable provocation test to examine the pituitary ACTH reserve and the integrity of the pituitary-adrenocortical axis; 2) isolated ACTH deficiency is usually due to a defect at the pituitary level; 3) with respect to adrenocortical responsiveness, post-Cushing's disease patients show a better accumulation of the provocative effect than do post-Cushing's syndrome patients; and 4) both hypothalamic and pituitary dysfunction are responsible for adrenal hypofunction in patients after hypercortisolemia, but post-Cushing's syndrome patients (especially those with a short period of hypercortisolemia) appeared to have less impairment of hypothalamic ACTH-releasing activity than post-Cushing's disease patients.
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PMID:Effects of repetitive administration of corticotropin-releasing hormone combined with lysine vasopressin on plasma adrenocorticotropin and cortisol levels in secondary adrenocortical insufficiency. 217 83

This experiment was designed to test further the hypothesis that vasopressin is the major mediator of the ACTH response to activation of central alpha 1-adrenoceptors in the rat. The alpha 1-adrenergic agonist methoxamine was given intracerebro-ventricularly to conscious vasopressin-deficient (homozygous Brattleboro) and normal rats bearing venous and intracerebro-ventricular cannulae. Methoxamine stimulated the secretion of ACTH in the normal, but not in the vasopressin-deficient, rats. The data confirm that vasopressin, rather than CRH-41 or oxytocin, is the major hypothalamic peptide that mediates the effects of central alpha 1-adrenoceptors on the pituitary corticotrophs.
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PMID:Brattleboro rats have deficient adrenocorticotropin responses to activation of central alpha 1-adrenoceptors. 217 37

All aspects of POMC biosynthesis exhibit tissue-specific regulation. The single copy gene is highly expressed in anterior lobe (AL) corticotrophs and intermediate lobe (IL) melanotrophs of the pituitary gland and in the arcuate nucleus of the hypothalamus. POMC gene transcription in corticotrophs is induced by hypothalamic CRH and vasopressin and inhibited by adrenal glucocorticoids, while in melanotrophs it is predominantly regulated by beta-adrenergic neural input and dopamine. To identify the rat POMC (rPOMC) gene sequences necessary and sufficient to target expression and hormonal regulation in corticotrophs and melanotrophs, we generated 13 transgenic mice carrying rPOMC fusion genes. The genes consisted of 706 or 480 basepairs of rPOMC 5' flanking sequences ligated to either the E. coli LacZ gene encoding beta-galactosidase or the K1 mutant of the SV40 large T-antigen gene. Overall, half of the transgenic lines had reporter gene expression in their AL and IL in a pattern indistinguishable from ACTH immunohistochemistry. In three of these lines, beta-galactosidase or K1 T-antigen was localized by double immunofluorescence exclusively to ACTH-positive corticotrophs and melanotrophs. Transcriptional regulation of the rPOMC-LacZ fusion gene in response to hormonal manipulation was quantified by a fluorescence assay for beta-galactosidase enzyme activity in pituitary extracts. There was a 15-fold increase in AL enzyme activity after adrenalectomy and a 3-fold increase in IL activity after haloperidol treatment. X-gal histochemistry of pituitaries from hormonally treated mice confirmed the cellular specificity of these effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pituitary-specific and hormonally regulated gene expression directed by the rat proopiomelanocortin promoter in transgenic mice. 217 40

We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH), 1 micrograms/kg growth hormone releasing hormone (GRH), 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms luteinizing hormone releasing hormone (LH-RH), and a relatively small dose (5 mU/kg) of lysine vasopressin (LVP). In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH) induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH), prolactin (PRL) and follicle-stimulating hormone (FSH) responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.
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PMID:Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors. 220 Feb 36

Previous studies have suggested the subfornical organ (SFO) to be the CNS site at which circulating angiotensin (ANG) acts to influence a variety of regulatory control mechanisms. We have utilised electrophysiological techniques: 1. to examine the neural connections through which the SFO exerts such control over hypothalamic regulatory control centres; 2. to investigate the responsiveness of neurons in a second circumventricular organ, the area postrema (AP), to circulating peptides. In accordance with previous endocrine studies we have demonstrated excitatory influences of SFO efferents on hypothalamic neurosecretory neurons putatively identified as vasopressin, oxytocin, CRH, and LHRH secreting. In addition systemic ANG increased the activity of the former three groups of these neurons, an effect which was abolished by destruction of the SFO. Single unit recordings from AP neurons have demonstrated subpopulations of cells in this regions to be sensitive to either circulating ANG or changes in blood pressure.
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PMID:Circumventricular structures: CNS sensors of circulating peptides and autonomic control centres. 236 60

Several peptide hormones are effective when administered intranasally (in); these include oxytocin, vasopressin, insulin, glucagon, and calcitonin. With regard to GHRH and CRH, previous studies demonstrated that their bioavailability following in administration was very low. In this study we evaluated the serum GH response to 50 micrograms GHRH iv and to 700 micrograms GHRH in, the latter given alone and with 5 and 15 mg sodium-glycocholate (SGC), a surfactant, in six normal men. The bioavailability of in GHRH, calculated as net GH secretory area, was very low, and increased to 7% that of iv GHRH when SGC was used. In the same men, 50 micrograms CRH was administered both iv and in, alone and with 5 and 15 mg SGC. The bioavailability of in CRH, calculated as net cortisol secretory area, was very low and increased to 100% that of iv CRH when 15 mg SGC was used. These data indicate that the efficacy of GHRH and CRH administered in is significantly augmented by SGC.
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PMID:Effect of intranasal growth hormone-releasing hormone and corticotropin-releasing hormone administration on growth hormone and cortisol release: improved bioavailability by means of sodium-glycocholate. 249 80

A functional ultrastructural assay was used to determine the response of corticotropin releasing hormone (CRH) neurosecretory cells to short-term stress. Depletion of neurosecretory vesicles from axonal swellings in the external zone of the rat median eminence was used as a measure of functional activity. One hour of immobilization or 5 h of insulin-induced hypoglycemia caused marked depletion of vesicles from the vasopressin (VP)-containing CRH axons, but had no effect on the VP-deficient subpopulation of CRH axons. Injection of colchicine (100 micrograms) into the lateral ventricle also resulted in selective depletion of vesicles from the VP-containing subpopulation over the course of 5 h, with no depletion from the VP-deficient axons. By 24 h after injection of 100 micrograms colchicine, however, both the VP-containing and the VP-deficient axons were severely depleted of neurosecretory vesicles. These data demonstrate for the first time that the CRH neurosecretory system contains functionally distinct components, and that the VP secreting component may specifically mediate the ACTH response to short-term stress.
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PMID:Stress selectively activates the vasopressin-containing subset of corticotropin-releasing hormone neurons. 251 67

To study possible adrenergic modulation of pituitary-adrenal responses to insulin-induced hypoglycemia and CRH we examined the effect of nonselective alpha-blockade (phentolamine) and nonselective beta-blockade (propranolol) on plasma ACTH, cortisol, and vasopressin (AVP) responses to hypoglycemia and CRH in five normal men. Infusion of propranolol or phentolamine did not alter basal plasma ACTH or cortisol levels. The propranolol infusion enhanced the stimulatory effect of hypoglycemia on ACTH, cortisol, and AVP secretion and also enhanced the stimulatory effect of CRH on ACTH and cortisol secretion. Infusion of phentolamine inhibited hypoglycemia-induced ACTH and AVP secretion, but had no effect on the stimulatory effect of CRH on ACTH and cortisol secretion. The increments of plasma ACTH and cortisol induced by an almost maximal dose of CRH (1 microgram/kg) were smaller than those induced by hypoglycemia. The propranolol-induced enhancement of the ACTH response to hypoglycemia was almost the same as the ACTH response to CRH alone. From these results we conclude that propranolol may act at the pituitary level to enhance CRH action, rather than AVP action, and that the ACTH response to hypoglycemia may be mediated by hypothalamic alpha-adrenergic activation.
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PMID:Adrenergic modulation of adrenocorticotropin responses to insulin-induced hypoglycemia and corticotropin-releasing hormone. 253 53


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