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)

Somatostatin analogs are an alternative medical treatment in patients with TSH-secreting pituitary adenoma. A 31-yr-old infertile woman with a TSH-secreting macroadenoma was treated with continuous sc infusion of 300 micrograms octreotide/day. After 3 months, euthyroid status was restored, and pituitary magnetic resonance imaging showed a reduction of the macroadenoma. Subsequently, the patient was found to be pregnant, and octreotide was stopped after 1 month of gestation. Serum TSH and free thyroid hormone concentrations returned to pretreatment values. At 6 months of pregnancy, a visual field examination was abnormal, and a magnetic resonance imaging scan showed an enlargement of the pituitary adenoma. Reinstitution of octreotide treatment was associated with normalization of TSH and free thyroid hormone concentrations, a rapid improvement of visual fields, and a new reduction in the size of pituitary macroadenoma. Octreotide treatment was continued until an elective cesarean section was performed at 8 months gestation. Despite the presence of immunoreactive octreotide in the umbilical cord, neonatal thyroid parameters were normal, and a physiological rise in TSH with the increase in thyroid hormone concentrations occurred in the neonate. In conclusion, 1) octreotide treatment is effective in controlling TSH-secreting macroadenoma during pregnancy; 2) despite the transplacental passage of immunoreactive octreotide, physiological changes in thyroid parameters occur in the neonate, and 3) exposure of the fetus to octreotide during the first month as well as the last trimester of gestation did not induce any malformation or affect fetal development.
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PMID:Successful pregnancy in an infertile woman with a thyrotropin-secreting macroadenoma treated with somatostatin analog (octreotide). 877 94

With the technique of in vivo somatostatin (SRIF) receptor (sst) scintigraphy a variety of human sst-positive tumours can be visualised 24-48 h after intravenous injection of the radiolabelled (SRIF) analogue [111In-DTPA-D-Phe1]octreotide. This rather long residence time of radioactivity on tumours suggests that the radioligand is internalised by the tumour cells; literature data for normal pituitary and pancreatic islet cells agree with this. Internalised SRIF has been found to be associated with cytoplasmic organelles, especially the Golgi apparatus, lysosomes and secretory granules. We have found that mouse AtT20 and primary cultures of human growth-hormone-secreting pituitary adenoma cells internalised a high amount of radio-iodinated [Tyr3]octreotide. Since octreotide binds with high affinity to the sst2 and sst5 subtypes and because both sst subtypes are expressed in these cells, one or both subtypes may be involved in this process. We also found that unlabelled octreotide, SRIF-14 or SRIF-28 can increase the internalisation of the radioligand. These observations, together with other studies on the manipulation of sst expression, may help to optimise the uptake of radioligand in in vivo sst scintigraphy in humans and improve the potential effect of radiotherapy with radiolabelled (subtype-specific) SRIF analogues.
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PMID:Internalisation of isotope-coupled somatostatin analogues. 881 57

Scintigraphy with [111In-DTPA-D-Phe]-octreotide is a recently developed technique for imaging somatostatin receptors in many neuroendocrine tumors. A good correlation between high [111In-DTPA-D-Phe]-octreotide uptake and the response to octreotide therapy has been proved in TSH- and GH-secreting pituitary adenomas, while few and conflicting scintigraphic data on somatostatin receptors in non-functioning tumors have been reported in the literature. The present study presents the results obtained with [111In-DTPA-D-Phe]-octreotide scintigraphy in thirteen patients with GH-secreting pituitary adenoma, four patients with inappropriate TSH-secretion and twelve patients with non-functioning pituitary adenoma. Twelve out of the 13 patients with GH-secreting pituitary adenomas had a positive scan; moreover, in 5/6 patients with a GH-secreting microadenoma (tumor size range 5-8 mm) a positive scan was found. Two TSH-secreting macroadenomas had a positive scan while a negative scan was obtained for a TSH-secreting pituitary microadenoma and in a patient with non-neoplastic, inappropriate secretion of TSH. Finally, only 2/12 patients with non-functioning pituitary adenoma showed a positive scan. In conclusion, [111In-DTPA-D-Phe]-octreotide scintigraphy is a useful tool to confirm the presence of somatostatin receptors in selected patients with GH- and TSH-secreting pituitary adenoma. The role of [111In-DTPA-D-Phe]-octreotide scintigraphy in non-functioning pituitary tumors remains to be established, but it could be useful for octreotide treatment in patients who refuse surgery or who are poor surgical candidates.
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PMID:[111In-DTPA-D-Phe]-octreotide scintigraphy in functioning and non-functioning pituitary adenomas. 900 59

We reported previously that somatostatin inhibits the expression of the immediate early gene c-fos. Accordingly, we characterized the molecular mechanisms by which somatostatin inhibits c-fos gene expression. Because growth factors activate c-fos through a region of its promoter known as the serum response element [SRE; base pairs (bp) -357 to -276] we transfected rat pituitary adenoma cells (GH3) with plasmids containing the SRE or the SRE core fragment (bp -320 to -298) upstream of the luciferase reporter gene. Epidermal growth factor (EGF) stimulated SRE-luciferase activity, and this effect was inhibited by somatostatin and by the analog MK-678. Identical results were obtained with the SRE core plasmid, demonstrating that the sequence between bp -320 and -298 of the c-fos promoter is a somatostatin response element. Because the extracellular signal-regulated protein kinases (ERKs) induce the SRE via phosphorylation of transcription factors such as Elk-1, we examined the effect of somatostatin on ERK phosphorylation and activation. EGF stimulated tyrosine phosphorylation of ERK2, and MK-678 attenuated this effect. In experiments using in-gel kinase assays, MK-678 also inhibited EGF-stimulated ERK activity via a pertussis toxin sensitive pathway, and this effect resulted in inhibition of Elk-1 transcriptional activity. Our data suggest that one mechanism of somatostatin action involves inhibition of ERK activity, Elk-1 phosphorylation and transcriptional activation, and ultimately c-fos gene transcription.
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PMID:Molecular mechanisms for somatostatin inhibition of c-fos gene expression. 914 1

Few data are available on the visualization of somatostatin receptors in vivo in patients with thyrotropin (TSH)-secreting adenoma. We studied five patients with TSH-secreting adenomas using single-photon emission tomography (SPET) after administration of indium-111 pentetreotide. The intensity of 111In-pentetreotide uptake by the tumours was correlated with the degree of TSH suppression after a single administration of 100 microg octreotide s. c. Five patients (three women and two men) aged 27-46 years were investigated. Except for one patient with acromegaly, all had pure TSH-secreting tumours. One patient was previously untreated, while two had received octreotide, one antithyroid drugs, and one radioiodine. In all patients SPET demonstrated increased uptake of 111In-pentetreotide by the pituitary adenoma. The target to non-target ratio (T/nT) of 111In-pentetreotide uptake was higher than 10 in three patients. Administration of 100 microg octreotide s. c. caused a significant reduction in TSH levels from 4.8+/-1.4 mU/l to a nadir of 3.1+/-1.1 mU/l after 6 h (P<<0.001 by ANOVA). Suppression of TSH secretion ranged from 30% to 60% of the baseline value. The T/nT ratio showed a trend toward a direct relationship with the degree of TSH inhibition after acute octreotide administration (r=0.67; P=NS). Our study showed that 111In-pentetreotide scan visualized somatostatin receptors in all five of the patients with TSH-secreting pituitary adenomas, confirming the frequent presence of somatostatin receptors in these rare tumours, even though the correlation with the TSH inhibition after a single administration of octreotide did not reach significance.
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PMID:Indium-111 pentetreotide single-photon emission tomography in patients with TSH-secreting pituitary adenomas: correlation with the effect of a single administration of octreotide on serum TSH levels. 921 57

We present a 32-year-old male with a thyrotropin (TSH)-secreting pituitary microadenoma with normal alpha-subunit (SU) and/or alpha-SU/TSH molar ratio. An interesting feature of this patient is that the size of the pituitary tumor remained unchanged during a 6-year follow-up without treatment. The tumor was clearly visualized with somatostatin receptor imaging, indicating that it was somatostatin receptor-positive. Subcutaneous injection of 100 microg octreotide acetate three times daily resulted in significant reduction of TSH and free thyroid hormones 6 weeks after initiation of treatment. However, tumor size was not changed 3 months after initiation of octreotide therapy and thyroid hormones, but not TSH level, eventually increased in spite of increasing the octreotide dosage up to 600 microg/day. This led to discontinuation of treatment. The patient responded only temporarily to octreotide in spite of somatostatin receptors. This case further demonstrates that a normal alpha-SU and/or alpha-SU/TSH molar ratio cannot exclude the possibility of a TSH-secreting pituitary adenoma.
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PMID:A case of thyrotropin-secreting pituitary microadenoma with normal thyrotropin alpha-subunit level. 922 17

The effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on hormone release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7 prolactinomas, and 2 insulinomas were investigated. In the pituitary adenoma cultures, a comparison was made with the effects of the dopamine (DA) agonists bromocriptine and/or quinagolide. In 5 NFAs, 2 prolactinomas and 1 insulinoma somatostatin receptor (subtype) expression was determined by ligand binding studies and by in situ hybridization to detect sst1, sst2, and sst3 messenger RNAs (mRNAs). Four NFA cultures did not secrete detectable amounts of alpha-subunit, FSH, and/or LH. In the other cultures, hormone and/or subunit release was inhibited by DA-agonists (10 nM) in 9 of 11, by SS (10 nM) in 7 of 11, and by octapeptide SS-analogs (10 nM) in 3 of 10 cultures. In three NFA cultures, hormone release was sensitive to SS but not to SS-analogs. In all cultures, except for one, DA-agonists were the most effective in inhibiting hormone release. In the prolactinoma cultures, PRL release was inhibited by DA-agonists (10 nM) in 7 of 7, by SS in 4 of 4, and by octapeptide SS-analogs in 3 of 7 cultures. A dissociation between the effects of SS and SS-analogs was found in 3 cases. In the cultures sensitive to both bromocriptine and SS-28, bromocriptine was the most potent compound in 2 out of 4 cultures. In the 2 other cultures, both compounds were equally effective. In 2 insulinoma cultures, insulin release was inhibited by SS, and by octapeptide SS-analogs in only one. The presence or absence of an inhibitory effect by octreotide was in all cases in parallel with the presence or absence of the inhibitory effect by BIM-23014 and RC-160. Autoradiographic studies using [125I-Tyr0]SS28 showed specific binding in 4 of 5 NFAs, 1 of 2 prolactinomas, and 1 of 1 insulinoma. Specific [125I-Tyr3]octreotide binding was found in 2 of 5 NFAs, in 1 of 2 prolactinomas, and in the insulinoma. Two NFAs showed binding of SS28, but not of the sst2.5 specific ligand octreotide. The tumors showed variable sst1 and/or sst3 mRNA expression, whereas no sst2 expression was found. In conclusion, a dissociation between the inhibitory effects of SS on the one hand and of the octapeptide SS-analogs octreotide, BIM-23014 and RC-160 on the other hand, is observed in a small subgroup of NFAs, prolactinomas, and insulinomas, suggesting that novel sst subtype specific SS-analogs might be of benefit in the treatment of selected patients with somatostatin receptor positive secreting tumors not responding to octapeptide SS-analogs. However, in the majority of NFAs and prolactinomas, DA-agonists were equally or more effective than SS in the suppression of tumoral secretion products.
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PMID:Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release in a small subgroup of pituitary- and islet cell tumors. 928 35

GH secreting pituitary adenomas are frequently visualized by scintigraphy with the somatostatin analogue 111Indium-pentetreotide. We studied 111Indium-pentetreotide scintigraphy and hormonal responses to octreotide in 12 acromegalic patients. Nine patients with active acromegaly were studied before pituitary adenomectomy; 6 of these and 3 other patients were studied after operation. GH was measured after a single s.c. dose of 100 micrograms of octreotide (acute test). The patients were preoperatively treated with 100 micrograms s.c. tid octreotide for 3 months as were patients who had been unsuccessfully operated; GH and IGF-I were measured at the end of this period (chronic treatment). A decrease of the hormones higher than 50% of basal values was considered a positive response in both acute test and chronic treatment. Eight/nine unoperated patients had a pituitary adenoma visualized by scintigraphy and a positive response to both the acute test and chronic treatment; one patient had no evidence of tumor at scintigraphy and he did not respond to octreotide. Scintigraphy was negative in all of the three patients cured by surgery. Six patients still had active disease after adenomectomy: scintigraphy was positive only in one case, although GH responded to octreotide treatment in all patients. Conclusions. 111In-pentetreotide scintigraphy frequently visualizes pituitary adenomas and predicts GH responses to octreotide in unoperated acromegalic patients. In unsuccessfully operated patients scintigraphy is infrequently positive and does not predict which patients will respond to octreotide. These data and the cost of 111In-pentetreotide scintigraphy do not warrant its extensive clinical use in acromegaly.
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PMID:111Indium-pentetreotide pituitary scintigraphy and hormonal responses to octreotide in acromegalic patients. 930 42

Previously, we have shown somatostatin receptor (SSTR) subtype-specific regulation of growth hormone (GH), thyroid-stimulating hormone, and prolactin (PRL) secretion in human fetal pituitary cultures, where GH and thyroid-stimulating hormone are mediated by both SSTR2 and SSTR5, whereas SSTR2 preferentially mediates PRL secretion. We now tested SSTR subtype-selective analogues in primary human GH- and PRL-secreting pituitary adenoma cultures. Analogue affinities determined by membrane radioligand binding in cells stably expressing human SSTR forms were either SSTR2 or SSTR5-selective. Analogues preferential either for SSTR2, including octreotide, lanreotide, and novel compounds with improved affinity for SSTR2, or new SSTR5-selective compounds suppressed GH in tumor cell cultures (up to 44% of control; P < 0.0005). However, novel analogues from both groups were 30-40% more potent than octreotide and lanreotide in suppressing GH (P < 0.05). Heterologous analogue combinations containing both SSTR2- and SSTR5-selective compounds were more potent in decreasing GH than analogues used alone (P < 0.05), or than combinations of compounds specific for the same receptor subtype (P < 0.005). In contrast, SSTR2-selective analogues did not suppress PRL release from six cultured prolactinomas studied. However, new SSTR5-selective analogues suppressed in vitro PRL secretion (30-40%; P < 0.05) in four of six prolactinomas. These results suggest that both SSTR2 and SSTR5 are involved in GH regulation in somatotroph adenoma cells, whereas SSTR5 exclusively regulates PRL secretion from prolactinoma cells. Thus, somatostatin analogues with improved selective binding affinity for these receptor subtypes may be effective in the treatment of either GH- or PRL-secreting adenomas.
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PMID:Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. 941 Sep 19

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


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