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)

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

Twenty-one patients with active acromegaly and two patients with pituitary gigantism were treated with the long-acting somatostatin analogue octreotide (100-600 micrograms/day, sc, two or three times daily or 300-1500 micrograms daily by intermittent sc infusion) for 9-63 months. There was rapid clinical improvement. The fasting plasma GH levels were significantly suppressed (less than 50% of the values before treatment) in 17 patients and were normalized (less than 5 ng/ml) in 6 patients (27.3%). Plasma IGF-I levels were lowered by 50% and were normalized in 7 out of 18 cases. The effect of octreotide on pituitary tumor size was evaluated in 13 patients. In 4 cases, the shrinkage of the pituitary tumor was detected by computed tomographic scans and/or magnetic resonance imaging studies. The drug was generally well tolerated. However, there were probably newly formed gallstones in two patients during the therapy. Our study suggests that octreotide is an effective and relatively safe new approach for treating active acromegaly and gigantism.
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PMID:[Long-term treatment of acromegaly and gigantism with octreotide (SMS 201-995)]. 159 44

A 2 1/4-year-old boy with pituitary gigantism had a large pituitary macroadenoma. Gross tumor removal has prevented further visual losses, but he has had persistent hypersecretion of growth hormone and prolactin. Treatment with somatostatin analog has decreased both hormone secretion and growth velocity.
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PMID:Pituitary gigantism caused by growth hormone excess from infancy. 159 54

Acromegaly and hyperprolactinemia have been reported in association with the McCune-Albright syndrome, but the pathophysiology of the GH and PRL hypersecretion that occurs in patients with this disorder has not been defined. We studied GH and PRL secretory dynamics in three patients with McCune-Albright syndrome and hypersecretion of these hormones. Each patient had excessive linear growth, glucose-non-suppressible plasma GH concentration, and GH responsiveness to TRH and GHRH. In response to exogenous GHRH, plasma GH concentrations rose approximately 2-fold in all three patients. Plasma GHRH levels were 20-40 ng/L (normal, less than 30). Study of the spontaneous GH secretory pattern in two patients indicated nocturnal augmentation of GH release. Bromocriptine therapy failed to reduce plasma GH in all patients; in one patient treatment with octreotide, a long-acting somatostatin analog, partially suppressed plasma GH and insulin-like growth factor I levels. These results suggest that hypersecretion of GH in the McCune-Albright syndrome is not due to ectopic GHRH production or autonomous somatotroph function. The results are similar to those described in classic acromegaly due to GH-secreting pituitary tumors. However, the lack of radiographic pituitary enlargement, the variable pituitary pathology reported in similar patients, and frequent concordance of GH and PRL excess suggest that the pathogenesis of this disorder may differ fundamentally from other forms of acromegaly or gigantism. The pathophysiology may reflect abnormal hypothalamic regulation and/or an embryological defect in pituitary cellular differentiation and function.
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PMID:Hypersecretion of growth hormone and prolactin in McCune-Albright syndrome. 249 85

Sixty-four patients with active acromegaly and three patients with gigantism were treated with the long acting somatostatin analog SMS 201-995 (50-500 micrograms, sc, every 6-12 h or 150-880 micrograms daily by intermittent sc infusion, for up to 114 weeks). The fasting plasma GH levels were significantly suppressed (less than 50% of the values before treatment) in 49 patients and became normal in 18 patients. Suppression of GH secretion was associated with normalization of plasma somatomedin-C levels (14 out of 30 cases) and significant clinical improvement such as disappearance of headache and decrease of excessive sweating. Shrinkage of pituitary tumors as determined by computed tomography and/or magnetic resonance imaging studies occurred in 11 out of 40 cases. Side effects were minimal and tolerable. SMS 201-995 appears to be an effective agent for the treatment of acromegaly and gigantism.
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PMID:[A multicenter clinical trial of SMS 201-995 (octreotide acetate) in acromegaly and gigantism]. 268 94

The case of a 16 year-old boy with McCune-Albright's syndrome which is rarely accompanied by gigantism was studied endocrinologically. The stimulation of growth hormone (GH) release by hypoglycemia, the decline of elevated GH by hyperglycemia and a little lower somatostatin like immunoreactivity (SLI) may support abnormalities of hypothalamic function, but the existence of pituitary microadenoma cannot be ruled out because of the paradoxical suppression of GH release by oral administration of bromocriptine (CB-154) and L-DOPA and the stimulation of GH release by intravenous administration of TRH.
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PMID:Gigantism associated with McCune-Albright's syndrome. 393 58

The in vivo bioactivity of ectopic growth hormone-releasing factor (GHRF) was examined in estrogen-primed, urethane-anesthetized male rats bearing intracarotid catheters. Ectopic GHRF was isolated from a carcinoid tumor metastatic to the liver from a patient with gigantism and elevated plasma growth hormone (GH) levels and was partially purified by reverse phase high performance liquid chromatography for intracarotid injection. Ectopic GHRF elicited a promt rise in plasma GH which peaked at 5 min. The time course of the response resembled that to prostaglandin E1, a known potent direct stimulator of GH secretion in vivo. The effect of ectopic GHRF was dose related in the range of 10-100 U/rat which represents approximately 30x the effective in vitro dose range/10(5) cells in rat adenohypophyseal cell cultures. The in vivo response to ectopic GHRF was completely blocked by the simultaneous intracarotid administration of the GH release inhibitory peptide, somatostatin. These findings lend further support for a role of GHRF from human tumors as a potent physiological stimulator of GH release.
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PMID:Ectopic growth hormone-releasing factor stimulates growth hormone secretion in the urethane-anesthetized rat in vivo. 641 54

The pathophysiology of mammosomatotroph adenomas remains unclear. We studied a mammosomatotroph adenoma removed from an 8-year old boy with a 5-year history of growth acceleration and acromegalic gigantism at presentation. Elevated basal GH (mean 28 micrograms/l) and PRL (mean 120 micrograms/l) plasma levels were observed, as well as paradoxical responses of GH to L-dopa, TRH and oral glucose administration; PRL was reduced by L-dopa and slightly increased by TRH; GHRH stimulated release of both GH and PRL. Two operations were required to remove the very large tumour and the patient was treated with bromocriptine before the second. Hormonal secretion by tumour explants in culture was evaluated under basal conditions and after stimulation or inhibition. High levels of GH and PRL were secreted for up to 24 days. Furthermore, GHRH and TRH caused a dose-related stimulation of both hormones, while somatostatin and dopamine were effective in suppressing either basal or stimulated hormone release only at very high (microM) concentrations. Intracellular events were studied by determination of the guanosine triphosphate binding (G) protein levels and adenylate cyclase (AC) activity in the tumour tissue. Before bromocriptine treatment, AC activity was very high in the tumour and could be further stimulated by various agents; very high levels of the AC-stimulatory G protein alpha subunit Gs alpha and very low amounts of the AC-inhibiting G protein alpha subunit Gi3 alpha and of the phospholipase C-stimulating G protein alpha subunit Gq alpha were found in the tumour. After bromocriptine, baseline AC activity was normalized and could no longer be stimulated; Gs alpha and Gi3 alpha levels were unchanged while those of Gq alpha were normalized. Screening of tumour DNA after amplification by polymerase chain reaction followed by single-strand conformational polymorphism analysis did not reveal any mutations in the hot spots of G protein alpha subunits (alpha s, alpha i2, alpha o2 and alpha 11) genes or in the H-ras and p53 genes. Gs alpha and GH transcription factor-1 (pit-1) expression were evaluated by amplification of cDNA. While the mRNA expression of pit-1 decreased after bromocriptine treatment, that of Gs alpha increased. These data suggest the possibility of an oncogenic process involving overexpression of Gs alpha, resulting in chronic activation of adenylate cyclase. Furthermore, our results suggest that the anti-secretory and anti-proliferative effects of bromocriptine may be mediated through a decrease in Pit-1 secondary to the inhibition of adenylate cyclase activity.
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PMID:Mammosomatotroph adenoma causing gigantism in an 8-year old boy: a possible pathogenetic mechanism. 762 75

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.
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PMID:Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma. 1036 9

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.
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PMID:Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma. 1099 42


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