Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The common obesity of middle age presents a set of features that strongly resembles the cardinal symptoms of Cushing's syndrome: obesity of the face (moon face), upper back (buffalo hump) and trunk (pot belly) accompanied by signs of protein-wasting. In non-obese individuals who remain at a constant weight throughout life, the proportion of adipose tissue increases with age at the expense of lean tissue loss. Thus, a mild version of Cushing's syndrome may be part of the normal aging process. A more intense version of this process may occur in overweight adults. Excess and chronic activity of two pituitary hormones may contribute to this adiposity. Both hormones are produced in the same pituitary cell by cleavage from a common large precursor known as pro-opiocortin. One hormone is adrenocorticotrophin (ACTH), which stimulates the release of the glucocorticoid hormones. These hormones promote the conversion of bodily proteins to glucose (gluconeogenesis). The other pituitary hormone is beta-endorphin, a stimulant of appetite that causes the release of insulin. This pancreatic hormone promotes the conversion of glucose and fatty acids to triglycerides (lipogenesis). Three different etiologies are suggested for the excessive and chronic action of these two pituitary hormones: tumors that increase the number of cells that synthesize pro-opiocortin; mutant strains that produce excessive amounts of ACTH and beta-endorphin such as the genetically obese mouse (ob/ob) and rat (fa/fa); and an age-determined shift in the type of cleavage enzymes present in the pro-opiocortin cell that favors ACTH and beta-endorphin production.
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PMID:The obesity of middle age: a common variety of Cushing's syndrome due to a chronic increase in adrenocorticotrophin (ACTH) and beta-endorphin activity. 22 74

Transgenic mice that developed adrenocorticotropic hormone (ACTH)-producing pituitary tumors were generated with the polyoma early region promotor linked to a cDNA encoding polyoma large T antigen (PyLT). Light microscopic examination of the pituitaries showed normal morphology at 4 months of age, either unremarkable morphology or microadenoma formation at 9 months of age, and up to 5 mm large adenomas in clinically ill transgenic mice at 13-16 months of age. At age 9 months, transgenic mice weighed significantly more than corresponding control mice, but they began wasting at approximately 1 year of age. The adrenal glands of these older PyLT-1 mice showed a weight increase and exhibited a medullary hyperplasia. Subcutaneous transplants of transgenic pituitary tumors to nontransgenic, immunocompetent mice resulted in tumors with a morphology and ACTH immunoreactivity similar to the primary tumor. The effects of hypercorticotropism were more enhanced and occurred with a shorter latency in the mice carrying transgene pituitary transplants than in the PyLT-1 transgenic mice themselves. Moreover, these transplanted mice showed a weight increase with an axial deposition pattern and hypertrophy of the adrenal cortex that resembled the findings in human Cushing's disease. Plasma ACTH levels were significantly increased in clinically ill transgenic mice and even higher levels were found in the transplant mice. Thus, both murine models should be useful for studying Cushing's disease.
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PMID:Transgenic mice that develop pituitary tumors. A model for Cushing's disease. 131 82

The most common ectopic production of a pituitary hormone is the one of ACTH leading to Cushing's syndrome. Ectopic ACTH-hypersecretion is the cause of Cushing's syndrome in 10-15% of all cases. The ACTH-secreting tumours are often oat-cell carcinomas of the lung, less frequently pancreatic cancers, hypernephromas, or C-cell carcinomas of the thyroid. Some of these tumours may be benign or semi-benign as the rare carcinoid tumours and cause great problems in the differential diagnosis of ACTH-dependent hypercortisolism. Out of 173 of our patients with Cushing's syndrome observed in the last 12 years 21 were caused by ectopic ACTH-production. Of these 21 patients 13 have a small cell carcinoma of the lung. The ectopic ACTH-syndrome often has typical clinical features caused by the levels of ACTH and cortisol leading to hypocalcemic alkalosis with muscle weakness and wasting, carbohydrate intolerance, and hypertension with oedema. The survival time in many of these patients is not long enough to allow them to develop typical signs of Cushing's syndrome though they are often highly pigmented. These patients are easily diagnosed. However, patients with small tumours which do not cause very elevated ACTH-levels and who have the more typical clinical signs of full-blown Cushing's syndrome are difficult to recognize. For the differential diagnosis of ACTH-dependent Cushing's syndrome the corticotropin-releasing hormone (CRH) stimulation test and dexamethasone suppression test with high doses are helpful. In special cases the venous sampling procedure for ACTH-measurements is necessary, also CT or NMR is helpful. Ectopic CRH-production is a rare cause of ACTH-dependent Cushing's syndrome. Patients with ectopic CRH-production and consecutive ACTH-hypersecretion from the pituitary have not been studied extensively. There are especially no well documented results of the use of the CRH-stimulation test in vivo in this group of patients with Cushing's syndrome. On the other hand, in the documented cases, not only CRH-, but also ACTH-production was found in the tumours. So far, this rare cause of ACTH-dependent Cushing's syndrome has to be excluded or confirmed by the measurement of endogenous CRH-levels. But until now we have not been able to detect one single case of ectopic CRH-production using a sensitive homologous CRH-radioimmunoassay over a period of more than 8 years in which we have seen nearly 120 newly diagnosed patients with ACTH-dependent Cushing's syndrome. Only in the plasma and tumour tissue of two patients of other groups have we found high CRH-levels.
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PMID:Ectopic production of ACTH and corticotropin-releasing hormone (CRH). 132 73

Hypothalamic pituitary functions were studied in 25 patients before and 6 months after cranial irradiation with or without radiosensitizing chemotherapy for nasopharyngeal carcinoma. The estimated average total dose was 5,000 cGy to the hypothalamus and pituitary gland. The radiosensitizing chemotherapy used was endoxan, 4900 +/- 873 mg and/or methotrexate 113 +/- 30 mg. All patients had normal pituitary function before radiotherapy. Six months after radiotherapy, there was a significant increase in baseline serum thyrotropin (TSH) and follicle-stimulating hormone (FSH) levels. The TSH response to thyrotropin-releasing hormone (TRH) was significantly increased, suggesting primary hypothyroidism due to neck irradiation. The peak serum TSH response to TRH became delayed in 21 patients, suggesting a defect in TRH release. In male patients who did not receive radiosensitizing chemotherapy, the FSH response to luteotropic hormone-releasing hormone (LHRH) increased while the luteinizing hormone (LH) response decreased. But in male patients who also received radiosensitizing chemotherapy, both the FSH and LH responses to LHRH increased. The adrenocorticotropic hormone (ACTH) response to ovine corticotropin-releasing hormone (CRH) did not change, while the integrated cortisol response increased. The growth hormone (GH) response to growth hormone-releasing hormone (GRH) did not change. The GH response to insulin tolerance test (ITT) increased and may be explained by the more severe hypoglycemia induced by the same dosage of insulin after radiotherapy or the recovery from the previous wasting caused by radiotherapy. There was no significant increase in serum prolactin. In conclusion, we demonstrated impairment of the hypothalamus-pituitary-endocrine gland axes as early as 6 months after cranial irradiation with or without chemotherapy.
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PMID:Early effects of cranial irradiation on hypothalamic pituitary function. 197 95

To assess the adrenocortical response of premature infants to alterations in sodium balance, the postnatal course of plasma progesterone, 11-deoxycorticosterone, corticosteronoe, aldosterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol and cortisone was compared in healthy premature infants kept on low (1-2 mEq/kg per day) or high (3-5 mEq/kg per day) sodium diet. The mean birthweight (1470 g, range: 1210-1670 g vs 1410 g, range: 1130-1750 g) and mean gestational age (30.5 weeks, range: 29-32 weeks vs 30.2 weeks, range: 28-32 weeks) in the low and high sodium groups, respectively, were similar. Simultaneous steroid hormone measurements were made weekly up to the 5th week of life using mechanized Sephadex LH-20 multicolumn chromatography and standardized radioimmunoassays. It was demonstrated that in response to renal salt wasting and negative sodium balance there was a significant rise in plasma aldosterone concentration. The plasma levels of other individual corticosteroids generally declined with advancing age, the initial fall, however, was followed by a transient and insignificant but simultaneous increase in 11-deoxycortisol, cortisol, cortisone and corticosterone in prematures on low a sodium diet. This effect could be prevented by giving NaCl supplement. The NaCl-suppressible increase in adrenocortical activity may be the result of the combined effect of stress or angiotensin 11-induced adrenocorticotropic hormone (ACTH) release and/or prolactin-mediated enhanced adrenal response to ACTH.
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PMID:Postnatal course of plasma levels of adrenocortical steroids in premature infants with and without NaCl supplementation. 321

Renal phosphate wasting related to a tumor (oncogenous osteomalacia) is a rare disorder usually associated with benign mesenchymal tumors. In this article, the authors describe a man with renal phosphate wasting and the syndrome of inappropriate antidiuretic hormone associated with small cell carcinoma. Chemotherapy markedly reduced tumor burden and was associated with normalization of renal phosphate handling and serum sodium. With recurrence, renal phosphate wasting and the syndrome of inappropriate antidiuretic hormone developed again, with the additional complication of hypercortisolism secondary to ectopic corticotropin production. The authors report the rare occurrence of renal phosphate wasting with small cell carcinoma (5 previously reported cases) and the unique co-existence of this paraneoplastic syndrome with the syndrome of inappropriate antidiuretic hormone and ectopic corticotropin production.
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PMID:Case report: renal phosphate wasting, syndrome of inappropriate antidiuretic hormone, and ectopic corticotropin production in small cell carcinoma. 760 39

Twenty-one hydroxylase (21-OH)-deficient classic adrenal hyperplasia (CAH) and nonclassic adrenal hyperplasia (NCAH) are two of the most common genetic disorders known to man, yet the mechanism(s) resulting in steroid excess remains unclear. Overactivation of the hypothalamic-pituitary-adrenal (HPA) axis and increased ACTH secretion appear to be important mechanisms resulting in steroid excess in untreated patients, at least in the classic forms of the disorder. Nonetheless, most NCAH patients do not demonstrate overactivity of the HPA axis. A few of these patients may demonstrate a mild degree of ACTH hyper-responsiveness to corticotropin-releasing hormone stimulation, and up to 40% have radiologic evidence of adrenocortical hyperplasia and/or isolated adenomas, suggesting that some degree of chronic ACTH excess is present. Another mechanism resulting in adrenocortical excess in adrenal hyperplasia, and primarily in NCAH, follows the alteration in enzyme kinetics resulting from the mutation of 21-OH. The mutated enzyme product is less efficient than the wild type, resulting in an increased precursor to product ratio, independent of ACTH levels. Hence, progesterone (P4) and 17-hydroxyprogesterone (17-HP) levels in these patients may remain above normal even in the presence of excess glucocorticoid administration. Overactivity of the renin-angiotensin system may also be important in stimulating adrenocortical steroidogenesis in patients with salt-wasting and in some with simple virilizing CAH. Alterations in ovarian and gonadotropic function, with the appearance of a polycystic ovary-like picture, also contribute to the androgen excess of these patients. Functional ovarian abnormalities in patients with CAH or NCAH may relate to a number of causes, including prenatal masculinization of the hypothalamic-pituitary-ovarian (HPO) axis by adrenal androgens, continued disruption of the HPO axis by persistently elevated P4 or androgen levels, and/or a direct glucocorticoid effect. Finally, these data suggest that the measurement of P4 or 17-HP may not be the most accurate marker of therapeutic efficacy, and suppression of both the ovaries and adrenals may be necessary for optimum steroidogenic control.
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PMID:The 21-hydroxylase-deficient adrenal hyperplasias: more than ACTH oversecretion. 892 12

Human critical illness is characterized by protein hypercatabolism, preservation of fat depots and by immune dysfunction. Optimized parenteral or enteral feeding and other advanced, supportive therapies remain unable to prevent ensuing wasting of vital organs and muscles and deficient healing processes. The anterior pituitary gland is a prime regulator of human metabolism and immune function through the orchestrated secretion of hormones, including growth hormone, thyrotropin, gonadotropins, prolactin and corticotropin. Except for the latter hormone, the releasing activity of the pituitary tends to decrease with advancing age and this decline is thought to be one of the mechanisms underlying the gradual loss of anabolic drive, reparative processes and cellular defence in senescence. In this work, critical illness was documented to be consistently associated with a diminished level of activity in the different axes governed by the pituitary, except for the corticotropic axis. In addition, this aging pattern of pituitary function in critical illness was found to be aggravated by the infusion of dopamine, a common practice in intensive care medicine for newborns, children and adults. The latter observation launches the hypothesis that endogenous dopamine may participate in the pathogenesis of the pituitary dysfunction in critical illness. Finally, these findings establish a base to explore the therapeutic potential of pituitary hormones and their secretagogues to enhance recovery from severe illness.
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PMID:A senescent pattern of pituitary function during critical illness and dopamine treatment. 895 55

The circadian rhythms of plasma growth hormone (GH), insulin-like growth factor type I (IGF-I), cortisol, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and prolactin (PRL) were evaluated in 13 HIV-seropositive patients (8 males and 5 females; mean age [+/-SD], 30 +/- 5 years), classified as CDC C2. Sixteen clinically healthy subjects (9 males and 7 females; mean age [+/-SD], 32 +/- 8 years) were chosen as control group. Samples were taken every 4 hr from 04:00 to 20:00 and every 2 hr from 20:00 to 04:00. Plasma GH was evaluated by IRMA procedure, plasma IGF-I by RIA (after separation of soluble IGF-I from IGF-I-binding proteins, using acid-ethanol extraction), plasma cortisol by a solid-phase RIA, plasma ACTH by double-antibody RIA, and serum TSH and serum PRL by a solid-phase two-site fluoroimmunometric assay. Rhythmometric data were analyzed by single and population mean cosinor analysis; the comparison of the parameters of the rhythm between patients and controls was carried out by the mesor test and the amplitude-acrophase Hotelling test. Alterations of the circadian pattern of GH, IGF-I, cortisol, ACTH, TSH, and PRL were demonstrated in HIV-seropositive patients. In fact, the circadian profiles of these hormones were clearly flattened and no statistically significant 24-hr rhythm was detectable (with the exception of cortisol). These results are consistent with the hypothesis that alterations of the circadian temporal structure may already be present in HIV-seropositive patients without wasting and infectious complications.
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PMID:Circadian secretory pattern of growth hormone, insulin-like growth factor type I, cortisol, adrenocorticotropic hormone, thyroid-stimulating hormone, and prolactin during HIV infection. 931 Feb 92

Equine and canine Cushing's syndrome, both of which are the result of elevated cortisol levels, show some different pathogenetical and clinical features and require different therapeutical approaches. In older horses the equine Cushing's syndrome (ECS) is not uncommon. Nearly all cases result from excessive hormone production in cells of the pars intermedia of the pituitary. Besides elevated levels of adrenocorticotrope hormone (ACTH), high peripheral levels of pro-opiomelanocortin, beta-endorphines and alpha-melanocyte-stimulating hormone can be measured. In middle-aged and geriatric dogs, Cushing's syndrome is the most frequently diagnosed endocrinologic abnormality. 80-85% of cases are pituitary-dependent and 15-20% are caused by cortisol producing tumors of the adrenals. 90% of pituitary lesions can be identified as adenomas, which are localised in most cases in the pars distalis of the gland, but may occur rarely in the pars intermedia, too. Clinical symptoms in both species are characterised by wasting despite good appetite or polyphagia, reduction of muscle mass with altered fat deposition and lethargy. Whereas polydipsia/polyuria is a very common feature in dogs with Cushing's syndrome, in horses it is almost invariably a sign of concurrent secondary diabetes mellitus. A typical symptom in ECS is a continuously growing haircoat (hirsutism), whereas in canine Cushing's syndrome generalised alopecia may bring the owner to consult a veterinarian. The symptoms and diagnostic procedures in a 33-year-old mare are described. Useful diagnostic tests are reviewed with special attention to species differences in reacting to them. The therapeutic approach with dopamine-agonists such as bromocriptine and pergolide as well as cyproheptadine to ECS is reviewed.
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PMID:[Equine Cushing syndrome (ECS). Case report, review of its diagnosis and therapy and substantial differences from Cushing syndrome in dogs]. 962 47


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