Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results are presented of the studies on corticotropin, cortisol, beta-lipotropin, beta-endorphine, somatotropin, somatostatin, prolactin and thyrotropin secretion in 46 patients with active Icenko-Cushing's disease at the nearest and late periods after the treatment with an antiserotonin drug--cyproheptadine (peritol) combined with an adrenocortical secretion inhibitor--khloditan. The hormone basal levels and secretion under the action of stress, induced by insulin hypoglycemia or thyroliberin injection, were determined in the patients under examination by radioimmunoassay. In patients with an acute stage of the disease the blood beta-lipotropin, beta-endorphine, corticotropin, cortisol, somatostatin and prolactin concentrations are elevated, whereas those of somatotropin and thyrotropin are lowered. The hypothalamic, hypophyseal and adrenocortical response to stress or thyroliberin injection is reduced. THe combined treatment with khloditan and high doses of cyproheptadine led to pronounced clinical and hormonal remission in 55% of the patients. The blood beta-lipotropin, beta-endorphine, corticotropin, cortisol, somatostatin and somatotropin concentrations returned to normal. The blood prolactin and thyrotropin levels, as well as the response to thyroliberin injection remained disordered.
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PMID:[Dynamics of secretion of hypothalamo-hypophyseal system hormones in Itsenko-Cushing disease as affected by combination therapy]. 614 Jun 77

ACTH responsiveness in vitro to synthetic corticotropin-releasing factor (CRF), lysine-8-vasopressin, and cAMP was examined using superfusion of pituitary adenoma tissue and the nonadenomatous tissue from 16 patients with Cushing's disease. Sensitivity of adenomas to lysine-8-vasopressin and cAMP was similar to that of nonadenomatous tissues; however, sensitivity of adenomas to CRF was lower than that of nonadenomatous tissues in 7 of 16 patients. CRF-induced ACTH secretion from adenomas was inhibited by Ca2+-free medium in all instances and by dexamethasone and somatostatin in some. Angiotensins I and II stimulated ACTH secretion from both adenomas and nonadenomatous tissues, while angiotensin I-induced ACTH secretion was inhibited by angiotensin-converting enzyme inhibitor. These results suggest that the sensitivity of the pituitary corticotroph adenomas to CRF in some patients is low. This may be due to an abnormality of the step(s) before cAMP formation, such as the CRF receptor.
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PMID:Effects of corticotropin-releasing factor and other materials on adrenocorticotropin secretion from pituitary glands of patients with Cushing's disease in vitro. 614 54

Attenuated plasma GH secretion during sleep and blunted GH responses to provocative stimuli have been observed in patients with Cushing's disease. Synthetic porcine galanin elicits GH secretion when given alone, and enhances the GH response to GHRH in normal human subjects. The aim of our study was to investigate the effects of galanin on the GH response to GHRH in patients with Cushing's disease. We studied 5 female subjects with untreated active Cushing's disease caused by micro-pituitary adenomas (age 43 +/- 6.7 years; BMI 30 +/- 0.7 kg/m2). Four normal adult females, matched for age and body weight with the patients with Cushing's disease, were studied as controls. Subjects underwent in random order: (1) infusion of synthetic porcine galanin IV, 500 micrograms in 100 mL; (2) infusion of saline, IV, 100 mL. A bolus of human GHRH(1-29)NH2 (Geref, Serono, Italy), 100 micrograms in 1 mL saline, was injected IV at 0 minutes. Patients with Cushing's disease showed blunted GH peaks after GHRH (1.2 +/- 0.4 micrograms/L) during saline infusion, as compared to normal controls (24.6 +/- 4.6 micrograms/L; p < 0.05). During galanin infusion a significantly enhanced GH response to GHRH, as compared with saline infusion, was observed in control subjects (GH peak: 51.4 +/- 9.8 micrograms/L; p < 0.05), but not in patients with Cushing's disease (GH peak: 2.3 +/- 0.6 micrograms/L). GH levels were significantly lower both after saline and after galanin in patients with Cushing's disease as compared to normal controls. Our data demonstrate that galanin is not able to enhance the GH response to GHRH in patients with Cushing's disease. That galanin cannot reverse this effect suggests that the mechanism of action of galanin is not via a decrease in somatostatin release by the hypothalamus.
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PMID:Effect of galanin on the growth hormone (GH) response to GH-releasing hormone in patients with Cushing's disease. 768 69

1. Somatostatin may play a role in the inhibition of growth hormone (GH) response to GH-releasing hormone (GHRH) in hypercortisolism. To examine this hypothesis we studied the effect of pyridostigmine, a cholinergic agonist that decreases hypothalamic somatostatin, on the GH response to GHRH in 8 controls, in 6 patients with endogenous hypercortisolism (3 with Cushing's disease and 3 with adrenal adenomas) and in 8 patients with exogenous hypercortisolism (lupus erythematosus chronically treated with 20-60 mg/day of prednisone). Each subject received GHRH(1-29)NH2,100 micrograms iv twice, preceded by pyridostigmine (120 mg) or placebo, orally. 2. The GH response to GHRH was significantly blunted in all hypercortisolemic patients compared to controls both after placebo (GH peak, 5.8 +/- 1.6 vs 46.2 +/- 15.9 micrograms/l, mean +/- SEM) and after pyridostigmine (15.7 +/- 5.6 vs 77.2 +/- 19.8 micrograms/l). 3. The GH response was absent in endogenous hypercortisolemic patients compared to the exogenous group, both after placebo (2.2 +/- 0.3 vs 8.5 +/- 2.4 micrograms/l) and after pyridostigmine (4.9 +/- 2.5 vs 23.8 +/- 8.7 micrograms/l). The GH release after GHRH/pyridostigmine for the exogenous group was similar to the response of controls treated with GHRH/placebo. 4. These results confirm that the GH response to GHRH is blunted in hypercortisolism, although more pronounced in the endogenous group. Pyridostigmine partially reversed this inhibition in the exogenous group. Therefore, somatostatin may play a role in the inhibition of GHRH-induced GH release in exogenous hypercortisolemic states.
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PMID:Different effects of pyridostigmine on growth hormone (GH) response to GH-releasing hormone in endogenous and exogenous hypercortisolemic patients. 790 4

To further explore the differential effects of peripherally and centrally derived hypercortisolism on neurohormonal systems implicated in the pathophysiology of mood and cognitive disturbances, we examined the cerebrospinal fluid (CSF) concentrations of immunoreactive somatostatin (IR-SRIF) in patients with Cushing's disease and major depression and the relationship of these levels to CSF immunoreactive corticotropin-releasing hormone (CRH) concentrations and urinary free cortisol excretion. In particular, since CSF SRIF levels consistently have been shown to be reduced in depression, we wished to assess whether decreased centrally directed SRIF was more likely a primary or a secondary factor in the hypercortisolism of major depression. CSF SRIF levels were significantly reduced in 11 patients with documented Cushing's disease and in 1 patient with ectopic adrenocorticotropic hormone secretion as compared with both 41 healthy volunteers (19.4 +/- 2.9 vs. 37.4 +/- 1.5 pmol/l; p < 0.01) and 28 patients with major depression (30.2 +/- 2.4 pmol/l; p < 0.05), whose CSF SRIF levels were also significantly reduced as compared with controls (p < 0.05). CSF SRIF levels in the Cushing's disease patients correlated positively with CSF CRH (r = 0.64; p < 0.025), suggesting that either the sustained hypercortisolism in these patients and/or its suppression of central CRH secretion contributed to the reduction in SRIF. A more modest but significant correlation between CSF SRIF and CSF CRH was observed in the healthy volunteers (r = 0.37; d.f. = 37; p < 0.02); in the depressed patients, no linear relationship, but rather an inverted U-shaped relationship was found which significantly fit by a quadratic function (r2 = 0.90; d.f. = 22; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebrospinal fluid immunoreactive somatostatin concentrations in patients with Cushing's disease and major depression: relationship to indices of corticotropin-releasing hormone and cortisol secretion. 809 79

The effect of the long-acting somatostatin analog octreotide (SMS 201-995) on adrenocorticotropin (ACTH) secretion was studied in five patients with untreated Cushing's disease in vivo and in six human corticotropic adenoma cell cultures in vitro. For the in vivo study, 100 micrograms of octreotide sc was given 30 and 180 min after cannulation of the cubital vein and 100 micrograms of corticotropin-releasing hormone (CRH) was injected iv at 210 min. Serum ACTH and cortisol levels were measured for 390 min. In vivo, octreotide had no significant effect either on basal or CRH-stimulated ACTH levels and did not influence cortisol levels. The in vitro studies were conducted with corticotropic adenoma cell cultures derived from adenoma tissue obtained from six patients with Cushing's disease. In four of six cell cultures, octreotide (1 nmol/l-1 mumol/l) inhibited basal ACTH secretion in a dose-dependent manner. The inhibition ranged from 70 to 92% for 1 nmol/l octreotide to 14-46% for 1 mumol/l octreotide as compared to controls (100%). In three of three octreotide-responsive adenoma cell cultures investigated. CRH-stimulated ACTH secretion was suppressed by octreotide. Hydrocortisone pretreatment in vitro abolished the inhibitory effect of octreotide on ACTH secretion in one octreotide-responsive corticotropic adenoma cell culture. In conclusion, we showed that octreotide in most cases could inhibit the ACTH release from human corticotropic adenoma cells in vitro but had no suppressive effect on ACTH levels of patients with Cushing's disease in vivo. This discrepancy could be due to a somatostatin receptor down-regulation by cortisol at the hypercortisolemic state in vivo.
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PMID:Octreotide exerts different effects in vivo and in vitro in Cushing's disease. 813 Aug 85

The effects of somatostatin and its analogs have been studied in different subclasses of patients with Cushing's syndrome (due to Cushing's disease, ectopic corticotropin [ACTH]- and/or corticotropin-releasing hormone [CRH]-secreting tumors, or ACTH-independent Cushing's syndrome) and in patients with Nelson's syndrome. In most patients with untreated Cushing's disease, octreotide does not suppress ACTH release, a finding that is supported by in vitro studies. However, octreotide or somatostatin inhibits pathological ACTH secretion in Nelson's syndrome. Short-term octreotide treatment has caused a significant initial response (decreased serum cortisol, ACTH, and cortisoluria) in 24 of 38 (64%) patients with ectopic ACTH/CRH Cushing's syndrome, and long-term treatment caused a persistent response in 10 of 14 (71%) cases. Pentetreotide scintigraphy may help to identify those patients with ectopic ACTH/CRH tumors who will have an initial response to octreotide, and is useful for locating ectopic ACTH/CRH-secreting tumors and their metastases. To date, octreotide has been shown to temporarily suppress gastric inhibitory peptide (GIP)-induced cortisol secretion in GIP-dependent (ACTH-independent) Cushing's syndrome, but has not shown any therapeutic benefit in other forms of ACTH-independent Cushing's syndrome.
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PMID:Is there a role for somatostatin and its analogs in Cushing's syndrome? 876 91

Patients with pituitary adenomas present with hypersecretion syndrome(s), and/or pituitary failure(s), and/or signs of mass effect, or incidentally. Pituitary function evaluation, visual acuity and field check-up, and MRI or at least CAT are compulsory for diagnosis, and for therapeutic approach; surgery for Cushing's disease, dopamine agonists for prolactinomas, somatostatin analogs or surgery for thyrotroph adenomas, surgery and/or somatostatin analogs and/or radiotherapy in acromegaly, surgery with additional irradiation in most adenomas of other types, or even expectation in some instances.
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PMID:[Hypophyseal adenomas: functional and tumor evaluation and therapeutic approaches]. 897 71

Over the past decade, several advances have been made in our understanding of the molecular pathogenesis of pituitary adenomas, and novel diagnostic tests for the diagnosis and differential diagnosis of Cushing's syndrome have been developed. Although established in the late 1970s, measurement of UFC has emerged as the most sensitive and specific test to screen for and confirm the presence of Cushing's syndrome. The combined CRH/DST is potentially a useful adjunct in patients with probable pseudo-Cushing's syndrome and borderline elevated urinary cortisol levels. Improved assays for circulating ACTH levels are now used as the first test in differentiating ACTH-dependent from ACTH-independent sources. HDDST with the revised reference ranges for UFC currently remains the primary test for differentiating pituitary from ectopic ACTH secretion. However, the CRH test may replace the HDDST in the foreseeable future because of its lower rate of false-positive and false-negative results. IPSS has been established as an integral part of the evaluation of patients with suspected Cushing's disease and no conclusive (> 0.8 to 1 cm) pituitary adenoma. Advances in the radiolabeling of small peptides, such as somatostatin analogs, may facilitate the search for occult ectopic sources.
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PMID:Clinical and biochemical evaluation of Cushing's syndrome. 942 58

RECOMMENDED TREATMENTS: The different therapeutic strategies proposed for pituitary adenomas are relatively well-known thanks to numerous studies evaluating their effect on outcome. Unfortunately, large comparative clinical trials are difficult to construct due to the small number of cases of this rare condition. Therapeutic recommendations are thus generally based on the opinion of recognized experts. MICROADENOMA: Small (< 10 mm) prolactin-secreting adenomas should be treated surgically, generally by transsphenoidal adenomectomy, or medically by dopaminergic agonists: bromocriptin, quinagolide or cabergolin (the two latter drugs are more effective and better tolerated than their parent compound bromocriptin). MACROADENOMA: The expected success rate for surgical treatment of macroadenomas is low and dopaminergic agonists is generally recommended (including cases with visual impairment since the effect can be very rapid). Prolactin levels can be lowered and tumor volume reduced (in > 70% of cases). ACROMEGALY: Surgery is the firs intention treatment for acromegaly. In case of unsuccessful surgery (the criteria for "cure" are much more strict in 1998 than previously), somatostatin analog and/or hypothalamo-hypophyseal radiotherapy are recommended. Slow release formulations of somatostatin analogs can now be given by monthly (octreotide LP) or biweekly (lanreotide LP) injections. CUSHING'S DISEASE: Cure can be achieved in > 80% of cases with surgery, the first intention treatment of choice. If surgery is unsuccessful, radiotherapy can be proposed associated with anticortisol drugs (mitotane), if needed, while waiting for the late effect of radiotherapy. CLINICALLY SILENT ADENOMAS: Non-functional adenomas should be operated. Some propose adjuvant radiotherapy in all cases and others only if residual tissue persists post-operatively.
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PMID:[Treatment of pituitary adenoma]. 989 1


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