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)

In this review we discuss the physiological effects of somatostatin, which are mediated by specific receptor subtypes on different tissues. These observations have suggested new therapeutic possibilities for the use of the synthetic somatostatin analogues in the treatment of acromegaly as well as a number of other endocrine and non-endocrine disorders.
Pituitary 1999 Jun
PMID:The therapeutic value of somatostatin and its analogues. 1108 Nov 76

The aim of this study was to evaluate the efficacy of a 6-month treatment with lanreotide (LAN) (60-90 mg/month) alone and combined with cabergoline (CAB) (1.5-3 mg/week) in 10 acromegalic patients previously demonstrated to be poor responders to octreotide (OCT) (0.6 mg/day) alone and combined with quinagolide (CV) (0.6 mg/day). All patients had previously undergone unsuccessful surgery and none of them received radiotherapy. Immunohistochemistry showed intense positive GH staining in all adenomas, positive PRL staining in 5 adenomas and faint ACTH or FSH/LH positive staining in other 2 adenomas. Moderately elevated serum PRL levels (35 and 47 ng/ml) were recorded in two patients. Fasting plasma IGF-I and serum GH levels were assayed at baseline and 30, 60, 90 and 120 days after each treatment. Gallbladder ultrasonography and sellar MRI were performed before and after 6 months of OCT and LAN treatments. After OCT treatment circulating GH and IGF-I levels remained elevated in all patients, while after 3 months of combined OCT + CV treatment, serum GH levels were suppressed (below 2.5 ng/ml) in only 1 patient. Significant increase of the percent GH (83.9 +/- 4.3 vs. 70.3 +/- 5.6%, p < 0.01) and IGF-I suppression (54 +/- 4.4 vs. 45.3 +/- 5.7, p < 0.01) and decrease of the nadir of GH (8.5 +/- 1.2 vs. 14.6 +/- 1.9 ng/ml, p < 0.01) and IGF-I (400.9 +/- 32.8 vs. 462.1 +/- 45.1 ng/ml) were obtained with the combined treatment when compared to OCT treatment alone. After a 15-30 days wash-out, circulating GH and IGF-I levels significantly increased up to pretreatment level in all patients. After 6 months of treatment with LAN, suppression of serum GH was achieved in 1 patient, but no difference in GH (66.3 +/- 6.3%) and IGF-I (43.9 +/- 4.6%) suppression was recorded in comparison to OCT treatment. After 3 months of treatment with LAN combined with CAB, suppression of serum GH and normalization of plasma IGF-I levels was achieved in 4 and 5 patients, respectively. Percent suppression of GH (88.1 +/- 2.1%) and IGF-I (57.5 +/- 2.8%) was significantly greater with the combined treatment than with LAN treatment alone. In the 7 patients with evident residual mass no change was documented by magnetic resonance imaging (MRI). None of the patients withdrew LAN + CAB treatment for poor tolerance, one patient had mild hypotension. Sludge was shown after 6 months of LAN treatment in one patient without notable change after 3 months of LAN + CAB treatment. In conclusion, the treatment with dopaminergic drugs such as CV and CAB, significantly increased the efficacy of somatostatin analogs, and can be used in combined therapy in poorly responsive patients.
Pituitary 1999
PMID:Efficacy of combined treatment with lanreotide and cabergoline in selected therapy-resistant acromegalic patients. 1108 Nov 89

We herein review published findings on the clinical characteristics of acromegalic patients harboring pituitary somatotrophinomas expressing adenylyl cyclase activating gsp mutations and present an update of our own data on a large series of 176 patients with and without these oncogenes. Gsp oncogenes are the result of point mutations in either codon 201 or 227 of the Gs-alpha subunit of the Gs-protein which controls adenylyl cyclase. They result ultimately in increased intracellular cAMP levels and thus in excessive growth hormone (GH) secretion. Our large series has allowed us to characterise patients with mutations in codon 201 and the far rarer group possessing codon 227 defects. Both groups were compared with patients without gsp oncogenes. In accordance with previous findings, there was no statistically significant difference in age of the patients belonging to each group, the overall average tumor diameter nor in pre-operative serum GH levels, although the latter showed a tendency to be lower in patients with gsp oncogenes. The distribution of different types of response during an oral glucose tolerance test (no change, paradoxical rise or greater than 50% decrease in serum GH levels) did not differ between the 3 groups. However, the incidence of microadenomas was higher in acromegalics expressing gsp oncogenes in patients possessing mutations in codon 227. Additionally, the incidence of invasiveness was much lower (10% v. 33%) in those tumors with mutations in codon 227. Finally, previous in-vitro data indicating that gsp oncogene-expressing tumors may respond more efficiently to the somatostatin analogue, octreotide, have been confirmed by subsequent in-vivo studies showing a better reduction in serum GH levels in patients with gsp oncogenes. These latter findings suggest that presence of gsp oncogenes may be a marker for good reponsiveness to octreotide. Assessment of gsp oncogene status of surgically removed pituitary somatotrophinomas may thus be helpful in designing optimal medical therapies in those acromegalics requiring further post-operative management of the disease.
Pituitary 1999 May
PMID:Clinical correlates in acromegalic patients with pituitary tumors expressing GSP oncogenes. 1108 Nov 96

The use of somatostatin analogues for the treatment of acromegaly is now well established. Recently long-acting preparations of octreotide and lanreotide have been introduced. In this study we have assessed the efficacy and tolerability of the long acting somatostatin analogue octreotide LAR in patients with acromegaly, and compared it with lanreotide SR. Five patients with active acromegaly were recruited; they were treated with lanreotide SR for 6 months and then, following a wash-out period, received octreotide LAR for 6 months. They were assessed at baseline, 3- and 6-months, by clinical score, GH and IGF1. Adverse effects were carefully monitored. Both treatments effectively reduced GH and IGF1 levels. Four of five patients achieved a mean GH level of < 2.5 ng/ml with both drugs; with octreotide LAR only, these patients also had GH < 1 ng/ml after oral glucose loading. The clinical symptoms score improved significantly with octreotide LAR, as did the ring size; the clinical score correlated significantly with GH. Blood glucose was not adversely affected. All patients experienced minor GI symptoms with lanreotide SR, but less frequently with octreotide LAR. Both drugs caused biliary stasis and had a tendency to form biliary sludge. Octreotide LAR proved effective for the treatment of acromegaly and was well tolerated. Octreotide LAR had some advantages over lanreotide SR, although the differences were not great.
Pituitary 2000 Oct
PMID:Long-acting octreotide LAR compared with lanreotide SR in the treatment of acromegaly. 1114 97

These studies examined the importance of phospholipase Cbeta (PLCbeta) in the calcium responses of pituitary cells using PLCbeta3 knockout mice. Pituitary tissue from wild-type mice contained PLCbeta1 and PLCbeta3 but not PLCbeta2 or PLCbeta4. Both Galphaq/11 and Gbetagamma can activate PLCbeta3, whereas only Galphaq/11 activates PLCss1 effectively. In knockout mice, PLCbeta3 was absent, PLCbeta1 was not up-regulated, and PLCbeta2 and PLCbeta4 were not expressed. Since somatostatin inhibited influx of extracellular calcium in pituitary cells from wild-type and PLCbeta3 knockout mice, the somatostatin signal pathway was intact. However, somatostatin failed to increase intracellular calcium in pituitary cells from either wild-type or knockout mice under a variety of conditions, indicating that it did not stimulate PLCbeta3. In contrast, somatostatin increased intracellular calcium in aortic smooth muscle cells from wild-type mice, although it evoked no calcium response in cells from PLCbeta3 knockout animals These results show that somatostatin, like other Gi/Go-linked hormones, can stimulate a calcium transient by activating PLCbeta3 through Gbetagamma, but this response does not normally occur in pituitary cells. The densities of Gi and Go, as well as the relative concentrations of PLCbeta1 and PLCbeta3, were similar in cells that responded to somatostatin with an increase in calcium and pituitary cells. Calcium responses to 1 nM and 1 microM TRH and GnRH were identical in pituitary cells from wild-type and PLCbeta3 knockout mice, as were responses to other Gq-linked agonists. These results show that in pituitary cells, PLCbeta1 is sufficient to transmit signals from Gq-coupled hormones, whereas PLCbeta3 is required for the calcium-mobilizing actions of somatostatin observed in smooth muscle cells.
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PMID:Calcium responses to thyrotropin-releasing hormone, gonadotropin-releasing hormone and somatostatin in phospholipase css3 knockout mice. 1114 44

Elevation of circulating GH acts to feed back at the level of the hypothalamus to decrease GH-releasing hormone (GHRH) and increase somatostatin (SRIF) production. In the rat, GH-induced changes in GHRH and SRIF expression are associated with changes in pituitary GHRH receptor (GHRH-R), GH secretagogue receptor (GHS-R), and SRIF receptor subtype messenger RNA (mRNA) levels. These observations suggest that GH regulates its own synthesis and release not only by altering expression of key hypothalamic neuropeptides but also by modulating the sensitivity of the pituitary to hypothalamic input, by regulating pituitary receptor synthesis. To further explore this possibility, we examined the relationship between the expression of hypothalamic neuropeptides [GHRH, SRIF, and neuropeptide Y (NPY)] and pituitary receptors [GHRH-R, GHS-R, and SRIF receptor subtypes (sst2 and sst5)] in two mouse strains with alterations in the GH-axis; the GH receptor/binding protein gene-disrupted mouse (GHR/BP-/-) and the metallothionein promoter driven human GHRH (MT-hGHRH) transgenic mouse. In GHR/BP-/- mice, serum insulin-like growth factor I levels are low, and circulating GH is elevated because of the lack of GH negative feedback. Hypothalamic GHRH mRNA levels in GHR/BP-/- mice were 232 +/- 20% of GHR/BP+/+ littermates (P < 0.01), whereas SRIF and NPY mRNA levels were reduced to 86 +/- 2% and 52 +/- 3% of controls, respectively (P < 0.05; ribonuclease protection assay). Pituitary GHRH-R and GHS-R mRNA levels of GHR/BP-/- mice were elevated to 275 +/- 55% and 319 +/- 68% of GHR/BP+/+ values (P < 0.05, respectively), whereas the sst2 and sst5 mRNA levels did not differ from GHR/BP intact controls as determined by multiplex RT-PCR. Therefore, in the absence of GH negative feedback, both hypothalamic and pituitary expression is altered to favor stimulation of GH synthesis and release. In MT-hGHRH mice, ectopic hGHRH transgene expression elevates circulating GH and insulin-like growth factor I. In this model of GH excess, endogenous (mouse) hypothalamic GHRH mRNA levels were reduced to 69 +/- 6% of nontransgenic controls, whereas SRIF mRNA levels were increased to 128 +/- 6% (P < 0.01). NPY mRNA levels were not significantly affected by hGHRH transgene expression. Also, MT-hGHRH pituitary GHRH-R and GHS-R mRNA levels did not differ from controls. However, sst2 and sst5 mRNA levels in MT-hGHRH mice were increased to 147 +/- 18% and 143 +/- 16% of normal values, respectively (P < 0.05). Therefore, in the presence of GH negative feedback, both hypothalamic and pituitary expression is altered to favor suppression of GH synthesis and release.
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PMID:The growth hormone (GH)-axis of GH receptor/binding protein gene-disrupted and metallothionein-human GH-releasing hormone transgenic mice: hypothalamic neuropeptide and pituitary receptor expression in the absence and presence of GH feedback. 1118 26

Pituitary diseases are often unrecognized in the elderly, although if they can be at the basis of several pathological conditions. We report three clinical cases. Patient n. 1: 87 years old woman, in poor general condition. Thyroid function evaluation showed secondary hypothyroidism. Subsequent pituitary function evaluation demonstrated hypopituitarism with empty sella. The diagnosis was "hypopituitarism with secondary hypothyroidism and adrenocortical insufficiency, in empty sella" starting substitutive treatment with glucocorticoids and L-thyroxine, with improvement in her clinical conditions. Patient n. 2: 74 years old woman, with severe congestive heart failure. Her clinical history revealed hypothyroidism. An endocrine evaluation (in absence of therapy) demonstrated panhypopituitarism with secondary hypothyroidism and adrenocortical insufficiency in presence of empty sella. The patients was started on substitutive treatment and her conditions improved. Patient n. 3: 74 years old man with several atrial fibrillation episodes and hyperthyroidism. Thyroid function evaluation suggested secondary hyperthyroidism confirmed by the presence of a pituitary macroadenoma. The patient underwent surgical adenomectomy by trans-sphenoidal route. The clinical conditions of the patient improved, but a slight secondary hyperthyroidism was still present caused by the persistence of residual pathological tissue in the right cavernous sinus region confirmed by octreoscan suggesting the presence of a lesion endowed with somatostatin receptors. The patient was started on long acting octreotide treatment, which is still in progress. In conclusion, pituitary diseases pass often unrecognized in the elderly. Their prompt recognition and treatment can resolve dangerous situations for the patients.
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PMID:[Pituitary pathology in elderly patients admitted in a division of internal medicine. Description of 3 cases]. 1119 82

Pituitary tumours are a common type of intracranial neoplasm and, depending on the cell type of origin, have diverse endocrine and reproductive effects. The developmental biology of the different cell types is understood to result from a sequential activation of a cascade of transcription factors, and mutations in these factors result in various forms of hypopituitarism. Tumours in the pituitary gland arise from activation of dominantly acting oncogenes such as gsp, or from loss of function of a series of tumour suppressor genes such as MEN1. Abnormal patterns of DNA methylation may be implicated in the allelic losses that cause tumour suppressor gene silencing. The different clinically recognized types of pituitary tumour are currently treated by medical therapies such as dopamine and somatostatin agonists, surgery or radiotherapy. However, these treatments are not entirely satisfactory and recent advances in gene therapy may offer valuable new therapeutic opportunities for patients with aggressive tumours that fail to respond to traditional approaches.
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PMID:Pituitary tumours. 1122 62

We studied the effects of cortisol withdrawal and patterned replacement upon spontaneous GH secretion and circadian rhythmicity in 7 patients with Addison's disease. Hydrocortisone was administered in physiological daily total dosages, and all resulting plasma cortisol values were 2-15 micrograms/dl. It was given in 3 pulsatile modes: simulating "physiological" rhythm, "reverse" diurnal rhythmicity and "continuous" pulsatility. All modes of cortisol administration increased mean 24 h, GH pulse amplitude and interpulse GH levels. During saline infusions circadian GH rhythmicity was preserved, with GH being at its highest between 2400-0400 h. Administration of hydrocortisone in any mode did not modify circadian GH rhythmicity. We conclude: Cortisol replacement in physiological daily doses increases GH output in patients with Addison's disease by augmenting GH pulse amplitude and interpulse levels. This is likely due to the attenuation of hypothalamic somatostatin (SRIF) secretion by physiologic levels of cortisol. By inference, it implies that cortisol deficiency leads to diminution of GH output with low GH pulse amplitude, likely as a result of an augmented hypothalamic somatostatin secretion. However, circadian rhythmicity of GH secretion is glucocorticoid-independent.
Pituitary 2000 Nov
PMID:Growth hormone (GH) secretion in primary adrenal insufficiency: effects of cortisol withdrawal and patterned replacement on GH pulsatility and circadian rhythmicity. 1138 82

The cyclic somatostatin analog, octreotide, forms the mainstay of medical treatment for acromegaly. In addition to lowering circulating growth hormone levels and shrinking tumor size, octreotide may provide symptomatic relief of headaches associated with growth hormone secreting tumors. The majority of reported complications of octreotide therapy are gastrointestinal and metabolic. The present case illustrates the development of acute bilateral cavernous sinus syndrome with loss of eye movement bilaterally during octreotide therapy. Serial MRI examination suggest tumor infarction as the etiology. The symptoms resolved over 2 months as the tumor shrunk in size and growth hormone was dramatically reduced.
Pituitary 2000 Nov
PMID:Somatotropinoma infarction during octreotide therapy leading to bilateral cavernous sinus syndrome. 1138 84


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