Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low-renin hypertension is common and usually implies increased retention of sodium (Na(+)). In every case of known etiology, there is a mineralocorticoid-induced increase in number of epithelial Na(+) channels (ENaCs) in the collecting duct of the kidney, leading to a state of "hyperENaCactivity." In primary aldosteronism, a result of either an adrenal adenoma or bilateral adrenal hyperplasia, aldosterone itself mediates the increase in ENaC function. A severe form of low-renin hypertension in which a molecular mutation in ENaC prevents removal of the channel from the cell surface, known as Liddle's syndrome, results in increased net ENaC activity but, in this case, independently of an increase in aldosterone. Glucocorticoid remedial aldosteronism, an autosomal dominant form of primary aldosteronism, results from a "new" or chimeric gene for aldosterone synthase. Adrenocorticotropic hormone stimulates its expression as well as secretion of aldosterone. Apparent mineralocorticoid excess results from a molecular mutation that allows cortisol to bind to the mineralocorticoid receptor. Both glucocorticoid remedial aldosteronism and apparent mineralocorticoid excess result in an increase in the number of ENaCs. The question remains whether low-renin essential hypertension is related to an increase in ENaC activity. Low-renin hypertension is most common in black patients, who tend to have lower levels of aldosterone as well as renin, which are features that resemble those found in Liddle's syndrome. Preliminary findings suggest that black patients with low-renin hypertension who are resistant to standard antihypertensive therapy respond favorably to the addition of spironolactone, a mineralocorticoid receptor antagonist that reduces ENaC activity.
...
PMID:Low-renin hypertension: more common than we think? 1117 96

The diagnosis of Cushing's syndrome remains a challenge in clinical endocrinology. Cushing's syndromes are usually classified as dependent or independent from ACTH. In the first class are Cushing's disease, the ectopic corticotropin syndrome and the rare ectopic CRH syndrome. These ACTH-dependent Cushing's syndromes usually present diffusely hyperplastic adrenal glands. In the second class, are cortisol producing unilateral adrenocortical adenomas or carcinomas. New entities have recently emerged as bilateral adrenal hyperplasia not dependent from ACTH; their etiopathogenies are heterogeneous with illicit expressions at the adrenal level of functional receptors to various ligands: GIP, catecholamines, lutropin... The knowledge of such entities has to be taken into consideration in the diagnostic and management of ACTH independent Cushing syndromes.
...
PMID:[Cushing syndromes due to aberrant expression of functional receptors other than ACTH. A new organic hypercorticism syndrome entity]. 1124 1

With increasing case reports, it has been indicated that some cases with adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) show abnormal responses in cortisol to various stimulation tests. Here we report a case of AIMAH that showed an aberrant response to angiotensin II via AT1 receptor in cortisol hypersecretion. A 53-yr-old man was admitted to our division seeking further examinations for the possible diagnosis of Cushing's syndrome. He had hypertension, diabetes mellitus, and physical stigmata, such as moon face and central obesity. His plasma ACTH level was undetectable, and plasma cortisol level was high. Plasma cortisol showed no normal diurnal rhythm and was not suppressed after the administration of 8 mg of dexamethasone. Abdominal computed tomography demonstrated nodular enlargement of bilateral adrenal glands. He was diagnosed with Cushing's syndrome owing to AIMAH. An injection of arginine vasopressin (AVP) increased plasma cortisol and aldosterone levels, whereas ACTH remained undetectable. After 4 h in an upright position, plasma cortisol and aldosterone levels were increased. Pretreatment with candesartan, angiotensin II receptor AT1 antagonist, blocked the increase in plasma cortisol level. These results suggested a possibility of adrenal hypersensitivity to angiotensin II and AVP in cortisol secretion. Bilateral laparoscopic adrenalectomy was performed. The histological findings of the specimen were compatible with AIMAH. In summary, we have made the first report on a case of AIMAH with possible hypersensitivity to angiotensin II.
...
PMID:Case of adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with possible adrenal hypersensitivity to angiotensin II. 1157 27

The adrenal glands are a major source of steroid hormone biosynthesis. In normal physiology, the pituitary hormone corticotropin (ACTH) regulates the secretion of glucocorticoids via its G protein-coupled receptor (ACTHR), the product of the MC2R gene. Aldosterone is another major product of the adrenal gland; its regulation is controlled mainly by the renin-angiotensin system, although ACTH plays a role, too, especially under certain pathological conditions. The adrenal gland also secretes lesser amounts of androgens and intermediate metabolites of all these steroids. Unregulated secretion of any of these hormones can be caused by tumors, adrenocortical adenomas or carcinomas, and/or bilateral (or, rarely, unilateral) hyperplasia. Cortisol-producing hyperplasia of the adrenal glands is caused by two distinct syndromes, both of which have been directly or indirectly associated with protein kinase A signaling: (i) primary pigmented nodular adrenocortical disease (PPNAD) (a micronodular form of bilateral adrenal hyperplasia), either isolated (rarely) or in the context of Carney complex, is caused (in most cases) by mutations of the PRKAR1A gene; and (ii) ACTH-independent macronodular adrenal hyperplasia (AIMAH), or massive macronodular adrenal disease (MMAD), has been associated with aberrant (ectopic) expression, and presumably regulation, of various G protein-coupled receptors. AIMAH is a rare, sporadic condition affecting predominantly middle-aged men and women with an almost equal ratio (the latter in contrast to other forms of endogenous Cushing's syndrome). Some familial cases of AIMAH have also been described, and it appears that the pathophysiological phenomena underlying AIMAH may be present in the far more common, sporadic adrenocortical tumors and, perhaps, in the nodular growth detected in the adrenal glands of the elderly in the general population. Thus, the study of ectopic receptor expression and cAMP-dependent PKA activity in AIMAH may have wider implications for adrenal and, indeed, endocrine tumorigenesis.
...
PMID:Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease. 1211 80

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.
...
PMID:Aberrant receptor-mediated Cushing's syndrome. 1263 19

Polycystic ovary syndrome (PCOS) affects about 4 to 6% of women of reproductive age and accounts for at least 75% of hyperandrogenic patients. PCOS is diagnosed by the presence of oligo-ovulation and hyperandrogenism after the exclusion of related disorders, such as 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH). In turn, NCAH is a homozygous recessive disorder, diagnosed by a corticotropin-stimulated 17-hydroxyprogesterone (17-HP) level greater than10 ng/mL (30.3 nmol/L) and confirmed by genotyping of the CYP21 gene. The prevalence of NCAH is approximately 50 times less than that of PCOS, affecting between 1 and 10% of hyperandrogenic women, depending on ethnicity. However, it is generally difficult to distinguish NCAH from PCOS solely on clinical grounds, as both demonstrate varying degrees of hyperandrogenism and ovulatory dysfunction. Most PCOS patients have insulin resistance, in contrast to those with NCAH. Likewise, polycystic ovaries are observed in up to 40% of NCAH patients. Both disorders have a strong familial component. The only method that allows the separation of NCAH from PCOS patients is the measurement of 17-HP levels. In conclusion, PCOS and NCAH have differences in prevalence and pathophysiology. However, because the disorders have significant clinical and hormonal similarities, the measurement of 17-HP, preferably basally as a screening method, should be incorporated into the evaluation of all hyperandrogenic patients.
...
PMID:21-hydroxylase-deficient nonclassic adrenal hyperplasia: the great pretender. 1459 52

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.
...
PMID:Gene array analysis of macronodular adrenal hyperplasia confirms clinical heterogeneity and identifies several candidate genes as molecular mediators. 1476 69

Adrenocorticotropic hormone (ACTH)-independent hypercortisolism accounts for 15%-20% of cases of Cushing syndrome and always arises from primary adrenal disease. Computed tomographic (CT) and magnetic resonance (MR) imaging findings in 37 patients with primary adrenal Cushing syndrome were analyzed and correlated with pathologic findings. Hyperfunctioning adenomas (n = 24), together with functioning carcinomas (n = 10), accounted for 92% of cases. Adenomas had a significantly smaller mean size (3.5 vs 14.5 cm) and lower mean unenhanced CT attenuation value (11 vs 28 HU) than did carcinomas. The presence of necrosis, hemorrhage, and calcification favored a diagnosis of carcinoma. Six of 10 carcinoma patients had metastases at presentation. Two adenomas were seen within a myelolipoma, which was recognized at both CT and MR imaging due to its fat content, and two adenomas were of uncertain malignant potential. Bilateral disease--primary pigmented nodular adrenal dysplasia (PPNAD) (n = 2) and ACTH-independent macronodular adrenal hyperplasia (AIMAH) (n = 1)--had characteristic imaging features. In PPNAD, multiple tiny (2-5-mm) nodules were visible bilaterally, with no overall glandular enlargement and normal intervening adrenal tissue. In AIMAH, both glands were grossly enlarged and contained nodules up to 3 cm in diameter. Familiarity with the range of imaging appearances of the adrenal glands in primary adrenal Cushing syndrome may help establish the underlying diagnosis.
...
PMID:CT and MR imaging of the adrenal glands in ACTH-independent cushing syndrome. 1502 92

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.
...
PMID:Cushing's syndrome variants secondary to aberrant hormone receptors. 1538 Aug 9

Endogenous Cushing's syndrome can result from excess adrenocorticotropic hormone (ACTH; corticotropin) production by a pituitary adenoma (Cushing's disease) or by ectopic tumors secreting ACTH or corticotro- pin-releasing hormone (CRH). ACTH-independent Cushing's syndrome is caused by adrenocortical tumors or hyperplasias. Initial diagnosis is performed using 24-hour urinary free cortisol, low-dose dexamethasone tests, salivary cortisol, or night-time plasma cortisol values. A dexamethasone CRH test can discriminate between Cushing's syndrome and pseudo-Cushing's syndrome. If ACTH is elevated, combinations of high-dose dexamethasone tests, CRH/desmopressin tests, and pituitary magnetic resonance imaging can indicate a pituitary source. Discrimination from an ectopic ACTH tumor often requires inferior petrosal sinus sampling to confirm the ACTH source. If ACTH is low, adrenal computed tomography scan will identify the adrenal lesion(s) implicated. Some cortisol-producing adrenal tumors or, more frequently, bilateral macronodular hyperplasias, are under the control of aberrant membrane hormone receptors, or altered activity of eutopic receptors. The initial therapy of choice for patients with Cushing's disease is the selective transsphenoidal removal of the corticotroph adenoma; this induces remission in approximately 80% of patients, but long-term relapse occurs in up to 30% of these cases. The choice of second-line therapy remains controversial. Repeat surgery can be successful when residual tumor is detectable on magnetic resonance imaging, but carries a high risk of hypopituitarism. Bilateral adrenalectomy may be a better choice in patients without visible residual tumors, particularly in women desiring fertility. Radiotherapy combined with ketoconazole or radiosurgery was recently found effective, but longer-term evaluation of hypopituitarism and brain function is required. Current studies do not support the systematic use of prophylactic radiotherapy after bilateral adrenalectomy to decrease the risk of Nelson's syndrome; however, as soon as the residual tumor progresses, surgery and radiotherapy should be initiated. Various drugs which inhibit steroid synthesis (ketoconazole, metyrapone, aminoglutethimide, mitotane) are often effective for rapidly controlling hypercortisolism either in preparation for surgery, after unsuccessful removal of the etiologic tumor, or while awaiting the full effect of radiotherapy or more definitive therapy. Surgery is usually the treatment of choice for removal of cortisol-secreting adrenal tumors or ectopic ACTH/CRH-secreting tumors. The identification of aberrant adrenal receptors has recently allowed normalization of cortisol secretion by specific ligand receptor antagonists in limited cases of Cushing's syndrome secondary to bilateral macronodular adrenal hyperplasia. The long-term follow-up of patients treated for Cushing's syndrome should include the adequate replacement of glucocorticoids and other hormones, treatment of osteoporosis, and detection of long-term relapse of Cushing's syndrome.
...
PMID:Classic and recent etiologies of Cushing's syndrome: diagnosis and therapy. 1576 24


<< Previous 1 2 3 4 5 6 7 Next >>

---