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)

Twenty consecutive patients with adrenal Cushing's syndrome were studied with an in vivo protocol to determine the prevalence and diversity of the presence of ectopic or abnormal hormone receptors in their adrenal tissues. All six patients with bilateral ACTH-independent macronodular adrenal hyperplasia were found to have one or two abnormal adrenal receptors, including those for gastric inhibitory polypeptide, vasopressin (V1-vasopressin), beta-adrenergic agonists, LH/human CG, or serotonin 5-HT4. The presence of abnormal hormone receptors was found to be less frequently present in unilateral adenomas or carcinomas (3 of 14). The identification of abnormal adrenal hormone receptors can allow new pharmacological therapies of hypercortisolism. We suggest that the clinical screening for the presence of abnormal hormone receptors should be conducted in patients with adrenal Cushing's syndrome and, more particularly, in those with ACTH-independent macronodular adrenal hyperplasia, in the hope of offering medical therapy as an alternative to bilateral adrenalectomy.
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PMID:Are ectopic or abnormal membrane hormone receptors frequently present in adrenal Cushing's syndrome? 1106 96

Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenomas or bilateral macronodular adrenal hyperplasia; this syndrome results from the adrenal overexpression of the GIP receptor, which was found to be without an activating mutation. An increased stimulation of cortisol secretion following administration of vasopressin was also reported by several investigators in patients with adrenal Cushing's syndrome; this was linked to an increased expression or abnormal response of the V1-vasopressin receptor. We have conducted a prospective in vivo evaluation of 20 patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In 6 cases of macronodular adrenal hyperplasia, we have identified, in addition to 2 cases of GIP-dependent Cushing's syndrome, 4 other patients in whom cortisol production was regulated abnormally either by vasopressin, B-adrenergic receptor agonists, hCG/LH, or serotonin 5-HT-4 receptor agonists. In 13 patients with unilateral adrenal adenoma, an abnormal response to a mixed meal or to vasopressin was found in 3 cases, suggesting that the presence of ectopic or abnormal hormone receptors is less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists of the abnormal receptors.
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PMID:[Illicit hormone receptors in adrenal Cushing's syndrome]. 1135 92

Multiple alterations of G-protein-coupled receptors and G-proteins regulating intracellular transduction signal have been described in endocrine tumours. In Cushing's syndrome, aberrant or 'illicit' expression of membrane receptors (mainly G-protein-coupled receptors) has been observed in adrenal adenomas and adrenocorticotropic hormone (ACTH)-independent macronodular bilateral adrenal hyperplasia. The best characterized example to date is the aberrant expression of the gastric inhibitory polypeptide receptor that causes 'food-dependent hypercortisolism'. Aberrant expression of the luteinizing hormone, 2-adrenergic, interleukin receptors have also been reported. The level of expression of the vasopressin V1a receptor correlates with the direct (ACTH-independent) cortisol response to vasopressin.
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PMID:Aberrant receptor-mediated Cushing's syndrome. 1263 19

The principal modulators of the hypothalamic-pituitary-adrenal (HPA) axis are corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP). Corticotropin-releasing hormone is not exclusively produced in the hypothalamus. Its presence has been demonstrated at peripheral inflammatory sites. Ovulation and luteolysis bear characteristics of an aseptic inflammation. CRH was found in the theca and stromal cells as well as in cells of the corpora lutea of human and rat ovaries. The cytoplasm of the glandular epithelial cells of the endometrium has been shown to contain CRH and the myometrium contains specific CRH receptors. It has been suggested that CRH of fetal and maternal origin regulates FasL production, thus affecting the invasion (implantation) process through a local auto-paracrine regulatory loop involving the cytotrophoblast cells. Thus, the latter may regulate their own apoptosis. During pregnancy, the plasma level of circulating maternal immunoreactive CRH increases exponentially from the first trimester of gestation due to the CRH production in the placenta, decidua, and fetal membranes. The presence in plasma and amniotic fluid of a CRH-binding protein (CRHbp) that reduces the bioactivity of circulating CRH by binding is unique to humans. Maternal pituitary ACTH secretion and plasma ACTH levels rise during pregnancy-though remaining within normal limits-paralleling the rise of plasma cortisol levels. The maternal adrenal glands during pregnancy gradually become hypertrophic. Pregnancy is a transient, but physiologic, period of hypercortisolism. The diurnal variation of plasma cortisol levels is maintained in pregnancy, probably due to the secretion of AVP from the parvicellular paraventricular nuclei. CRH is detected in the fetal hypothalamus as early as the 12th week of gestation. CRH levels in fetal plasma are 50% less than in maternal plasma. The circulating fetal CRH is almost exclusively of placental origin. The placenta secretes CRH at a slower rate in the fetal compartment. AVP is detected in some neurons of the fetal hypothalamus together with CRH. AVP is usually detectable in the human fetal neurohypophysis at 11 to 12 weeks gestation and increases over 1000-fold over the next 12 to 16 weeks. The role of fetal AVP is unclear. Labor appears to be a stimulus for AVP release by the fetus. The processing of POMC differs in the anterior and intermediate lobes of the fetal pituitary gland. Corticotropin (ACTH) is detectable by radioimmunoassay in fetal plasma at 12 weeks gestation. Concentrations are higher before 34 weeks gestation, with a significant fall in late gestation. The human fetal adrenal is enormous relative to that of the adult organ. Adrenal steroid synthesis is increased in the fetus. The major steroid produced by the fetal adrenal zone is sulfoconjugated dehydroepiandrosterone (DHEAS). The majority of cortisol present in the fetal circulation appears to be of maternal origin, at least in the nonhuman primate. The fetal adrenal uses the large amounts of progesterone supplied by the placenta to make cortisol. Another source of cortisol for the fetus is the amniotic fluid where cortisol converted from cortisone by the choriodecidua, is found. In humans, maternal plasma CRH, ACTH, and cortisol levels increase during normal labor and drop at about four days postpartum; however, maternal ACTH and cortisol levels at this stage are not correlated. In sheep, placental CRH stimulates the fetal production of ACTH, which in turn leads to a surge of fetal cortisol secretion that precipitates parturition. The 10-day-long intravenous administration of antalarmin, a CRH receptor antagonist, significantly prolonged gestation compared to the control group of animals. Thus, CRH receptor antagonism in the fetus can also delay parturition. The HPA axis during the postpartum period gradually recovers from its activated state during pregnancy. The adrenals are mildly suppressed in a way analogous to postcure Cushing's syndrome. Provocation testing has shown that hypothalamic CRH secretion is transiently suppriently suppressed at three and six weeks postpartum, normalizing at 12 weeks.
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PMID:Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and postpartum. 1464 20

Increased hypothalamo-pituitary-adrenal activity contributes to morbidity in widespread metabolic and psychiatric diseases. Inhibition of hypercortisolism represents a promising therapeutic strategy in these conditions, which currently cannot be used. Here, we tested the hypothesis that atrial natriuretic peptide (ANP) administered intranasally is a safe and feasible inhibitor of pituitary-adrenal activity at the central nervous level. Thirty minutes after intranasal administration of ANP (1 mg) and placebo, pituitary-adrenal activity was stimulated in 18 healthy men by two tests: 1) a standard insulin-hypoglycemia test and 2) CRH combined with vasopressin (VP), respectively. ACTH, cortisol, VP, blood pressure, heart rate, and measures of fluid balance were also recorded. Pretreatment with ANP suppressed cortisol (P < 0.01) and ACTH (P < 0.05) secretory responses to insulin-induced hypoglycemia to about half of that seen after placebo, but pituitary-adrenal activity was not suppressed by CRH/VP injection (P > 0.7). Indicators of fluid balance, cardiovascular parameters, and self-report measures were not influenced by the treatment. Results indicate a strong inhibition of stimulated pituitary-adrenal activity after intranasal administration of ANP. The absence of an effect on CRH/VP-induced pituitary-adrenal responses suggests a direct action of the peptide on the central nervous system inhibiting stimulated hypothalamo-pituitary-adrenal activity at the hypothalamic level.
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PMID:Intranasal atrial natriuretic peptide acts as central nervous inhibitor of the hypothalamo-pituitary-adrenal stress system in humans. 1535 75

The successful treatment of Cushing syndrome depends on specific therapy directed against the etiology of hypercortisolism. In addition to surgical procedures, various drugs have been employed in the management of this difficult disease. Compounds with neuromodulatory properties have been effective in only a limited number of cases of hypothalamic-pituitary-dependent Cushing disease, the most common form of Cushing syndrome. These agents include serotonin antagonists (cyproheptadine, ketanserin, ritanserin), dopamine agonists (bromocriptine, cabergoline), GABA agonists (valproic acid [sodium valproate]), and somatostatin analogs (octreotide). Interesting new avenues at the pituitary level involve the potential use of thiazolidinedione compounds, such as rosiglitazone, and of retinoic acid, which are ligands of different nuclear hormone receptors involved in hypothalamic-pituitary regulation. The most exciting news, however, in the pharmacologic approach to Cushing syndrome refers to the adrenal corticotropin (adrenocorticotropic hormone; ACTH)-independent forms, in which aberrant adrenal receptors, through the binding of their respective ligands, could lead to chronic cortisol overproduction. They include receptors for gastric inhibitory peptide (GIP), beta-adrenergic agonists, luteinizing hormone (LH)/human chorionic gonadotropin, serotonin (5-HT(4) receptor), vasopressin (V(1) receptor), and angiotensin II (AT(1) receptor). In GIP-dependent Cushing syndrome, the most frequent subtype of ACTH-independent macronodular adrenal hyperplasia associated with the presence of aberrant adrenocortical hormone receptors described so far, octreotide administration before each meal showed clinical efficacy only in the first few months, probably because of somatostatin receptor downregulation in GIP-secreting cells. Long-term medical treatments with propranolol and the gonadotropin-releasing hormone analog leuprorelin (leuprolide acetate) were effective in patients with catecholamine-dependent and LH-dependent Cushing syndrome, respectively. The oral vasopressin V(1) receptor antagonist OPC-21268 and the angiotensin II (AT(1)) receptor antagonist candesartan cilexetil were also able to decrease cortisol levels during the few days of administration of the drugs in patients with specific receptor abnormalities. These adrenal forms of Cushing syndrome are rare, and clinical data are scarce. Moreover, the real clinical significance of aberrant hormone receptors is still under investigation, as is the possibility of avoiding surgery by pharmacologic manipulation. Patients in whom these intriguing syndromes are suspected require detailed investigation protocols, which should be carried out in specialized centers. While awaiting further developments, the use of traditional medical treatment at the adrenal level with adrenal steroid inhibitors is still valuable in several instances.
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PMID:Pharmacologic management of Cushing syndrome : new targets for therapy. 1578 46

Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.
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PMID:Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin. 1618 50

Pituitary adenomas often present with the symptoms of hormonal hypersecretion, and although medical therapy is available for most hyperfunctioning states, it is not curative. As a result, transsphenoidal pituitary surgery has become a commonly performed neurosurgical procedure with unique challenges for the anesthesiologist due to the distinct medical comorbidities associated with various adenomas. Any type of pituitary tumor may also produce hypopituitarism and local mass effects secondary to the expanding intrasellar mass. Here we review the perioperative concerns surrounding surgery to remove adenomas and decompress the sellar space. Special attention is given to Cushing's disease (hypercortisolism secondary to an adrenocorticotropic hormone-secreting adenoma), acromegaly (secondary to a growth hormone-secreting adenoma), and hyperthyroidism in the setting of thyrotropic adenomas. Operative risks, including bleeding, diabetes insipidus, the syndrome of inappropriate antidiuretic hormone secretion, and hypopituitarism, are addressed in detail. Understanding preoperative assessment, intraoperative management, potential complications, their management, and strategies for avoidance are fundamental to successful perioperative patient care and avoidance of morbidity and mortality.
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PMID:Perioperative management of patients undergoing transsphenoidal pituitary surgery. 1771 70

Desmopressin is a synthetic analogue of the hypothalamic peptide vasopressin and binds to specific pituitary vasopressin (V3) receptors. The V3-receptor is overexpressed in pituitary corticotrope tumors and the injection of desmopressin induces a marked ACTH and cortisol release in human patients with pituitary- (PDH), but not adrenal tumor (AT) dependent hyperadrenocorticism. In this prospective study, we investigated the effects of desmopressin on serum cortisol levels in 80 dogs suspected of Cushing's syndrome. The aim was to find a sensitive and specific test to exclude AT. According to standard tests the dogs were divided into 3 groups (group 1=other disease, n=27; group 2=PDH, n=46; group 3=AT, n=7). Desmopressin was injected as an i.v. bolus of 4microg and serial blood samples were collected before and after 30, 60 and 90min. Desmopressin significantly stimulated cortisol release in dogs with PDH (median 51%, range -24 to 563%; p<0.0001), whereas no increase was seen in dogs with AT (median -12%, range -44 to 5%; p=0.063) and in controls (median +7%, range -36 to 196%; p=0.131). Using a cut off value of 10% increase over baseline, it was possible to exclude AT in 75% of patients. The results of this study suggest that the desmopressin test could be a useful tool in differentiating pituitary from adrenal dependent Cushing's syndromes. Additional dogs with adrenocortical tumor must be tested in order to recommend its use in clinical practice.
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PMID:The desmopressin stimulation test in dogs with Cushing's syndrome. 1785 Oct 17

Cortisol secretion in ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing's syndrome can be controlled by illegitimate receptors. The aim of the present study was to characterize the molecular, immunohistochemical, and pharmacological profiles of vasopressin receptors in cells derived from three patients with AIMAH (H1-H3), in order to evaluate the role of ectopic vasopressin receptors in the physiopathology of hypercortisolism. Expression of mRNAs encoding the vasopressin receptor types (V(1a), V(1b), and V(2)) were analyzed by RT-PCR in adrenal tissues. The presence of V(1a) and V(2) receptors was studied by immunohistochemistry on adrenal sections. The pharmacological profiles of vasopressin receptors involved in the control of cortisol secretion were investigated using the V(1a) receptor antagonist SR49059 and the V(2) receptor agonist [deamino-Cys(1), Val(4), D-Arg(8)]-vasopressin on cultured cells. The V(1a) receptor protein was present and functional in H1 and H3 tissues, whereas the V(1b) receptor was not expressed in any of the tissues. RT-PCR experiments revealed that V(2) receptor mRNAs were detected in the three tissues. In contrast, immunohistochemical and cell incubation studies showed that the V(2) receptor was involved in the stimulatory effect of AVP on cortisol secretion in H1 and H2, but not in H3 cells. Taken together, these data show that expression of functional ectopic V(2) receptors and repression of eutopic V(1a) receptor can coexist in some hyperplastic corticosteroidogenic tissues. They also reveal that immunohistochemical and incubation studies are essential for the characterization of ectopic receptors actually involved in the control of cortisol secretion by AIMAHs.
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PMID:Expression of vasopressin receptors in ACTH-independent macronodular bilateral adrenal hyperplasia causing Cushing's syndrome: molecular, immunohistochemical and pharmacological correlates. 1818 Mar 12


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