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)

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. Gastric inhibitory polypeptide (GIP)-dependent Cushing's syndrome has been described in patients with either unilateral adenoma or bilateral macronodular adrenal hyperplasia; this syndrome results from the large adrenal overexpression of the GIP receptor without any activating mutation. We have conducted a systematic in vivo evaluation of patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we have identified, in addition to GIP-dependent Cushing's syndrome, other patients in whom cortisol production was regulated abnormally by vasopressin, ss-adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In patients with unilateral adrenal adenoma, the abnormal expression or function of GIP or vasopressin receptor has been found, but the presence of ectopic or abnormal hormone receptors appears to be 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 for the abnormal receptors.
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PMID:The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies. 1100 21

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

Cortisol secretion in adrenal Cushing's syndrome can be regulated by the aberrant adrenal expression of receptors for gastric inhibitory polypeptide, vasopressin, catecholamines, LH/human CG (LH/hCG), or serotonin. Four patients with incidentally discovered bilateral macronodular adrenal hyperplasia without clinical Cushing's syndrome were evaluated for the possible presence of aberrant adrenocortical hormone receptors. Urinary free cortisol levels were within normal limits, but plasma cortisol levels were slightly elevated at nighttime and suppressed incompletely after dexamethasone administration. Plasma ACTH was partially suppressed basally but increased after administration of ovine CRH. A 51-yr-old woman had ACTH-independent increases of plasma cortisol after 10 IU AVP im (292%), 100 microg GnRH iv (184%), or 10 mg cisapride orally (310%); cortisol also increased after administration of NaCl (3%), hCG, human LH, and metoclopramide. In a 61-yr-old man, cortisol was increased by AVP (349%), GnRH (155%), hCG (252%), and metoclopramide (191%). Another 53-yr-old male increased plasma cortisol after AVP (171%) and cisapride (142%). Cortisol secretion was also stimulated by vasopressin in a 54-yr-old female. This study demonstrates that subclinical secretion of cortisol can be regulated via the aberrant function of at least V1-vasopressin, LH/hCG, or 5-HT4 receptors in incidentally identified bilateral macronodular adrenal hyperplasia.
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PMID:Aberrant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome. 1170 32

Arginine vasopressin (AVP) stimulates cortisol secretion through its vascular type V(1a) receptor in the adrenal glands, in addition to stimulating ACTH secretion through pituitary V(3) receptor. Because hyper-response of plasma cortisol to vasopressin is documented in some patients with Cushing's syndrome due to adrenal adenoma (CS) or ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), we analyzed the expression of V(1a), V(2), V(3) receptor and AVP mRNA in human adrenal tissues by quantitative competitive RT-PCR or real-time PCRs. V(1a) receptor mRNA levels (ratio against glyceraldehyde 3-phosphate dehydrogenase) were 0.378 +/- 0.143 (mean +/- SE) in preclinical CS (n = 5) and 0.630 +/- 0.072 in AIMAH (n = 4), which were significantly higher than those (0.046 +/- 0.012; n = 9) in control adrenals, whereas those in overt CS (0.143 +/- 0.048; n = 10) or aldosterone-producing adenomas (0.069 +/- 0.018; n = 12) were similar to control adrenals. Although ectopic expression of V(2) or V(3) receptor was detected in half of AIMAH cases, the absolute levels were low. Furthermore, V(1a) receptor mRNA levels in the adjacent adrenal glands (0.190 +/- 0.039, n = 9) of aldosterone-producing adenomas were higher than those in control adrenals and in the corresponding tumor portions (0.079 +/- 0.024). In contrast, there were no significant differences in AVP mRNA levels among these groups. These results suggest that eutopic V(1a) receptor overexpression is involved in the etiology of AIMAH and a subset of adrenal adenomas causing overt or preclinical Cushing's syndrome. Our results imply a possible association of V(1a) receptor expression with adrenal hyperplasia.
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PMID:Eutopic overexpression of vasopressin v1a receptor in adrenocorticotropin-independent macronodular adrenal hyperplasia. 1246 75

In dexamethasone-suppressed healthy volunteers, the serotonin4 (5-HT4) receptor agonist cisapride and lysine vasopressin [LVP, an analog of arginine vasopressin (AVP)] have no influence on plasma cortisol levels (PCL). In contrast, cisapride and AVP have been shown to stimulate cortisol secretion in patients with adrenal tumor or bilateral adrenal hyperplasia and Cushing's syndrome. In this report, we describe a case of adrenocortical adenoma causing subclinical Cushing's syndrome. Cisapride and terlipressin, a precursor of LVP, both induced an increase in PCL reaching +88% and +100%, respectively, without any significant variation of plasma ACTH levels. In vitro experiments were conducted to investigate the effects of 5-HT and AVP on cortisol production from cultured tumor cells and normal adrenocortical cells. 5-HT and AVP both induced a dose-dependent increase in cortisol production from cultured tumor cells. Comparison of the data obtained with tumor and normal cells, respectively, showed that 5-HT was more efficient to stimulate steroidogenesis in adenomatous than normal cells. Concurrently, the efficacy and potency of AVP were both higher in tumor than normal cells. Collectively, these results show that the abnormal in vivo responses of the adrenocortical adenoma to cisapride and LVP could be ascribed to an increased sensitivity of the tumor tissue to 5-HT and AVP. The data also suggest that the adrenocortical tumor overexpressed eutopic 5-HT4 and V1 receptors.
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PMID:Effects of serotonin and vasopressin on cortisol production from an adrenocortical tumor causing subclinical Cushing's syndrome. 1253 Jun 99

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

Corticotropin (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is a heterogeneous condition in which cortisol secretion may be mediated by gastrointestinal peptide (GIP), vasopressin, catecholamines and other hormones. We studied the expression profile of AIMAH by genomic cDNA microarray analysis. Total RNA was extracted from eight tissues (three GIP-dependent) and compared to total RNA obtained from adrenal glands from 62 normal subjects. Genes had to be altered in 75% of the patients, and be up- or downregulated at a cutoff ratio of at least 2.0; 82 and 31 genes were found to be consistently up- and downregulated, respectively. Among the former were regulators of transcription, chromatin remodeling, and cell cycle and adhesion. Downregulated sequences included genes involved in immune responses and insulin signaling. Hierarchical clustering correlated with the two main AIMAH diagnostic groups: GIP-dependent and non-GIP-dependent. The genes encoding the 7B2 protein (SGNE1) and WNT1-inducible signaling pathway protein 2 (WISP2) were specifically overexpressed in the GIP-dependent AIMAH. For these, and six more genes, the data were validated by semiquantitative amplification in samples from a total of 32 patients (the original eight, six more cases of AIMAH, and 18 other adrenocortical hyperplasias and tumors) and the H295R adrenocortical cancer cell line. In conclusion, our data confirmed AIMAH's clinical heterogeneity by identifying molecularly distinct diagnostic subgroups. Several candidate genes that may be responsible for AIMAH formation and/or progression were also identified, suggesting pathways that affect the cell cycle, adhesion and transcription as possible mediators of adrenocortical hyperplasia.
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PMID:Gene array analysis of macronodular adrenal hyperplasia confirms clinical heterogeneity and identifies several candidate genes as molecular mediators. 1476 69

The secretion of cortisol and other steroids from adrenal tumors can be regulated by hormones other than corticotropin following the aberrant expression of several G-protein-coupled receptors (GPCRs). To date, ectopic receptors for gastric inhibitory polypeptide, beta-adrenergic receptor agonists, vasopressin (V(2) and V(3) receptors), 5-hydroxytryptamine (5-HT(7) receptor) and, probably, angiotensin II (AT(1) receptor) have been identified. Either increased expression or altered activity of eutopic receptors for vasopressin (V(1)), luteinizing hormone/human chorionic gonadotropin, 5-HT (5-HT(4) receptor) and leptin might also be involved. One or more aberrant receptors can be present in unilateral tumors and bilateral macronodular adrenal hyperplasia, at either the early subclinical or overt stages of hormone secretion. The identification of aberrant adrenal GPCRs offers the potential for novel pharmacological therapies that either suppress the endogenous ligands or block the receptor with specific antagonists.
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PMID:Cushing's syndrome variants secondary to aberrant hormone receptors. 1538 Aug 9

ACTH-independent, cortisol-producing hyperplasia is caused by 2 distinct disorders, primary pigmented nodular adrenocortical disease (PPNAD) and ACTH-independent macronodular adrenal hyperplasia (AIMAH). We will review recent findings on the clinical and molecular aspects of PPNAD and AIMAH. Inactivating mutations of PRKAR1A on 17q22-24, which codes for the type 1A regulatory subunit of protein kinase A, have been found in a subgroup of patients with PPNAD with and without Carney complex. AIMAH is a rare condition in which cortisol secretion may be mediated by non-ACTH circulating hormones such as gastric inhibiting polypeptide (leading to food-dependent Cushing's syndrome), vasopressin, catecholamines, luteinizing hormone, serotonin, angiotensin-II or leptin. The primary etiology of AIMAH remains unclear. Recently, we studied the expression profile of AIMAH by genomic cDNA microarray analysis. Several candidate genes were identified, suggesting pathways that affect the cell cycle, adhesion and transcription as possible mediators of adrenocortical hyperplasia.
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PMID:Clinical and molecular genetic studies of bilateral adrenal hyperplasias. 1566 94


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