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 hypothalamic regulatory hormones used for clinical studies are TRH, Gn-RH and somatostatin. In addition, as dopamine appears to be a physiological PIF, the dopamine agonists such as bromocriptine, could be considered as functional analogues of PIF. Gn-RH can be used to study the hypothalamic-pituitary gonadal relationship and to test the secretory reserve capacity of the gonadotrophs in disease states. Unfortunately Gn-RH testing discrimulates between pituitary and hypothalamic diseases only poorly. However gonadotrophin deficient men or women may be successfully treated with long-term Gn-RH with induction of puberty, potency, spermatogenesis and ovulation. Somatostatin has multiple actions in inhibiting endocrine and exocrine secretion but its actions are still being explored in diabetes. Bromocriptine, a long acting dopamine agonist (a functional analogue of PIF), suppresses prolactin and is highly effective in treating many hypogonadal states since hyperprolactinaemia is common. It also lowers growth hormone in acromegaly. TRH has provided a major, accurate, sensitive and safe test of thyroid function.
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PMID:Hypothalamic regulatory hormones: physiological and clinical implications. 2 68

Oral glucose tolerance tests (OGTT) were performed for two subsequent days in 4 patients with active acromegaly, 2 patients with prolactin-producing pituitary adenomas and one insulinoma patient. Thirty minutes before the second OGTT 250 mug of somatostatin were injected intravenously as a bolus followed by a somatostatin infusion (500 mug) over 21/2 hours. The OGTTs were pathologic due to the hGH- and hPRL-induced insulin antagonism; they could not be normalized or improved by somatostatin. Only the peak of the blood sugar curve was shifted from one to two and a half hours after glucose administration; insulin and hGH levels were regularly suppressed after somatostatin whereas hPRL remained unchanged in most instances. Gastrin levels increased in all patients during the OGTT, the increase was suppressed in 4 patients. These findings show that the pathologic glucose tolerance due to insulin antagonism could not be improved by somatostatin in contrast to the deteriorated glucose tolerance in insulinopenic states.
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PMID:[Influence of somatastatin on oral glucose tolerance in autonomous hypersecretion of growth hormone, prolactin or insulin (author's transl)]. 17 8

A present considered concept of growth hormone secretion is that the hormone is tonically inhibited by the hypothalamic tetradecapeptide somatostatin. The episodic fashion of GH secretion with 6-8 GH peaks per 24 hours and its modulation by light and sleep are probably governed by factors other than somatostain, one possibly being melatonin. Evidence for a GH-releasing factor also exists, causing a basal release pattern of GH in moderate hourly peaks. The regulotary peptides in their turn, and possibly the GH producing cell itself, are influenced by dopaminergic or noradrenergic neurons. GH secretion is also modulated in a not yet elucidated relation to serotonin activity. Furthermore, GH induced somatomedin may constitute a negative feed-back on the pituitary and/or hypothalamic level. In acromegaly and gigantism, conditions characterized by chronic hypersecretion of GH, the GH producing cells are less differentiated as indicated by their response with GH release to unphysiological stimuli as well as their cessation of GH release to stimuli that normally act as releasors of GH.
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PMID:Regulation of growth hormone secretion during normal conditions and in patients with acromegaly. 27 37

The effect of somatostatin on the thyrotropin (TSH), prolactin, growth hormone (GH) and insulin responses to the combined administration of thyrotropin releasing hormone (TRH) and arginine was studied in six healthy subjects, three hypothyroid patients and three acromegalic patients. Similar inhibition by somatostatin of the TSH and insulin responses was observed in the three groups. While the tetradecapeptide had no significant effect on the prolactin response in the healthy and acromegalic subjects, it caused an unexpected inhibition of the prolactin response in two of the hypothyroid subjects. Contrary to the findings in the healthy and hypothyroid subjects, somatostatin did not inhibit the GH response in the acromegalic patients. Normal inhibition by somatostatin of the insulin response, followed by a rebound in insulin secretion, was observed in all subjects. These preliminary data indicate increased sensitivity of the prolactin-secreting cells to somatostatin in hypothyroidism and suggest that decreased responsiveness of the somatotrophs to somatostatin could play a role in the pathogenesis of acromegaly.
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PMID:Effect of somatostatin on thyrotropin, prolactin, growth hormone and insulin responses to thyrotropin releasing hormone and arginine in healthy, hypothyroid and acromegalic subjects. 40 75

Glucagon is secreted not only by A2-cells of the pancreatic islets but also by A cells in the gastric fundus and duodenum. Several reports have demonstrated that the glucagon plasma concentration is increased in genetic diabetes as well as in many conditions associated with a decreased glucose tolerance such as hepatic cirrhosis, myocardial infarction, infectious diseases, burns, taumatic shock, glucagonomas, acute pancreatitis, acromegaly, pheochromacytoma and Cushing's syndrome. Hyperglucagonemia is particularly important in diabetic ketoacidosis and in non-ketotic hyperosmolar coma. The mechanisms responsible for the diabetic's hyperglucagonemia remain controversial. According to several authors, the increased glucagon secretion is, for its main part, secondary to a prolonged defect in insulin secretion and thus relatively insensitive to an acute insulin administration. According to others, the A cell abnormality is of primary origin, independant from insulin deficiency and its effects are cumulative with those of the insulin lack. Several reports dealing with induced or spontaneous experimental diabetes are in favor of the first or the second hypothesis. It appears likely that glucagon plays a role in the metabolic derangments of diabetes. Indeed, hepatic glucose production is closely related to the ratio of molar concentrations of insulin and glucagon. Finally, in insulin-dependant diabetics, somatostatin infusion reduces plasma glucagon concentration and blood glucose and prevents the development of ketosis after withdrawal of insulin therapy. These results illustrate the contribution of glucagon in the pathogenesis of hyperglycemia and ketosis. Several arguments have been accumulated in favor of the following concept: diabetes hyperglycemia results both from glucose under-utilization secondary to insulin lack and from hepatic glucose over-production due to glucagon excess. Although controversial, the role of glucagon in ketogenesis appears likely.
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PMID:[The role of glucagon in hyperglycemia. A review (author's transl)]. 79 28

Thirteen patients with acromegaly were subjected to the examination of autonomity in growth hormone (GH) secretion. TRH (500 mug iv), arginine (0.5 g/kg of body weight iv infusion), LH-RH (100 mug iv) and L-dopa (500 mg orally) were administered, and plasma GH was measured. Among them, 11 patients showed some response in plasma GH to at least one agent, but the other 2 cases showed no response to any of the above 4 agents. In the former 11 cases, the patients were regarded as belonging to the less autonomous type and in the latter 2, to the more autonomous type in GH secretion. Six cases (4 cases of the less autonomous and 2 cases of the more autonomous type) received an administration of 500 mug of synthetic somatostatin parenterally. Following administration of somatostatin, the patients of both types showed significant GH decrease, although GH decrease in the more autonomous type was smaller than that of the less autonomous type. These results would suggest that there might be no acromegalics secreting GH FROM THE PITUITARY WITH COMPLETE AUTONOMITY, AND THE DIFFERENCE OF AUTONOMITY IN ACROMEGALIC PATIENTS MIGHT DEPEND EITHER ON THE DIFFERENCE IN SENSITIVITY AND/OR THE NUMBER OF RECEPTORS IN THE PITUITARY RATHER THAN THOSE IN HYPOTHALAMUS TO EXOGENOUS STIMULI.
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PMID:Differences in autonomity of growth hormone secretion in patients with acromegaly. 82 58

The synthetic linear tetradekapeptide somatostatin (growth-hormone release inhibitory hormone: GHRIH) inhibits the liberation of growth hormone in normal persons in the insulin hypoglycaemia test without influencing the rise of cortisol and prolactin, while the concentrations of LH, FSH and TSH remain unchanged. In patients with florid acromegaly there occurs during administration of GHRIH a marked fall in the raised STH level without influencing the basal level of the other anterior-pituitary hormones. As a further effect there is suppression of the insulin level. The somatostatin at present available has a very short biological half-life and in its present form is, therefore, without therapeutic importance.
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PMID:[The effect of synthetic somatostatin in normal and acromegalic males]. 109 Apr 28

The acute suppressive effects of L-dopa and somatostatin (growth hormone release inhibiting hormone) on the elevated plasma GH concentrations of seven patients with acromegaly were compared. In addition the effects of the two agents on fasting concentrations of plasma glucose, insulin, glucagon and prolactin were studied. In six of the seven patients hourly samples for GH assay were taken from 08.00 to 20.00 hours on a control day. Synthetic cyclic somatostatin (100 mug) was infused intravenously in an albumin/saline solution over 75 min with a Harvard constant infusion pump. Levodopa 500 mg was given orally. Somatostatin infusion produced a reduction in plasma GH concentrations in six of seven patients (mean reduction 55%). L-Dopa produced a reduction in plasma GH concentrations in the same six patients (mean reduction 52%). The minimum GH concentrations achieved in the two tests were comparable and did not differ significantly from the minimum GH concentrations recorded during the 12 h control study. Mean plasma insulin and glucagon concentrations were also significantly reduced during the somatostatin infusion (P less than 0-025; P less than 0-05 respectively). Plasma glucose concentrations did not change. L-Dopa did not alter mean plasma glucose, insulin or glucagon values. Somatostatin did not alter prolactin values but L-Dopa suppressed basal values to less than 2 ng/ml in five patients. This study shows that the plasma GH change after the administration of L-dopa and somatostatin in acromegaly is comparable and confirms the pancreatic effects of somatostatin.
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PMID:A comparison of the effect of levodopa and somatostatin on the plasma levels of growth hormone, insulin, glucagon and prolactin in acromegaly. 126 63

As the long-acting somatostatin analog octreotide attenuates polypeptide hormone hypersecretion, it has recently been used to effectively treat acromegaly and gastrointestinal carcinoid tumors. Most growth-promoting actions of GH are mediated by insulin-like growth factor-I (IGF-I), which circulates complexed with multiple binding proteins (IGFBPs). IGFBP-1, a nonglycosylated peptide, competes with the IGF-I receptor for ligand binding and also regulates IGF action. To examine GH-independent mechanisms for octreotide regulation of the GH axis, circulating levels of IGFBP-1 were measured hourly after sc octreotide or saline administration in normal and GH-deficient adults. As IGFBP-1 is inhibited by insulin and GH, the dynamic pattern of alterations in GH and insulin levels was also assessed. After octreotide (100 micrograms) administration to 10 normal subjects, mean IGFBP-1 concentrations were stimulated from 23 +/- 4 to 72 +/- 18 micrograms/L (P < 0.007 vs. saline) after 2 h. Maximal induction of IGFBP-1 levels occurred after 3 h (325 +/- 115 micrograms/L; P < 0.02 vs. saline) and remained elevated (P < 0.005) for 6 h. IGFBP-1 was induced by octreotide in all subjects and was confirmed by Western ligand blotting. Insulin and GH levels preceding the rise in IGFBP-1 were unaltered by octreotide. Octreotide stimulated IGFBP-1 5-fold during a sustained fast in 4 normal subjects, despite equally suppressed insulin levels in both saline- and octreotide-treated groups. In 4 GH-deficient adults, IGFBP-1 levels were stimulated by octreotide from 16 +/- 3 to 146 +/- 36 and 154 +/- 28 micrograms/L after 3 and 4 h, respectively. In conclusion, the somatostatin analog octreotide induces IGFBP-1 independently of GH and insulin. As IGFBP-1 regulates the action of IGF-I, octreotide stimulation of IGFBPs may represent an additional pharmacological mechanism for attenuating the GH-IGF-I axis.
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PMID:Octreotide stimulates insulin-like growth factor-binding protein-1: a potential pituitary-independent mechanism for drug action. 128 85

The development of a long-acting somatostatin (SRIH) analog (octreotide, Sandoz) has been a major breakthrough in the treatment of acromegaly. However, in 20-30% of the patients, growth hormone (GH) plasma levels remain elevated (> 10 micrograms/l) despite treatment with octreotide. This raised the concept of resistance to SRIH analog therapy in acromegaly. Indeed, in vivo response to SRIH analogs varies greatly among acromegalic patients. According to the reviews in the literature and our own autoradiographic data, no direct correlation can be established between the GH response to octreotide and the number or affinity of the SRIH receptors located on the tumor. In our series a greater density of SRIH receptors is present on tumors from patients very sensitive to the SRIH agonist. A subset of patients resistant to octreotide could result from a very low density of SRIH receptor although this type of GH-secreting tumor constitutes certainly a rare case. A subset of GH-secreting pituitary tumors can be characterized by a mutation on the alpha subunit of the guanine nucleotide-dependent protein coupled to the stimulation of adenylate cyclase (G alpha s). This mutation results in a high basal adenylate cyclase activity and a low GHRH-stimulated activity. However, when the adenomas are separated according to their basal adenylate cyclase activity, SRIH is able to decrease cAMP levels in both types of tumor. In addition, in our series no direct correlation is observed between the SRIH inhibition of adenylate cyclase and the amount of SRIH-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Resistance to somatostatin (SRIH) analog therapy in acromegaly. Re-evaluation of the correlation between the SRIH receptor status of the pituitary tumor and the in vivo inhibition of GH secretion in response to SRIH analog. 130 25


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