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 objective of the study was to determine the tolerability and effectiveness of the slow release (SR) somatostatin analog lanreotide in active acromegaly. Fifty-seven patients, unselected in terms of their previous responsiveness to octreotide therapy, were included in a prospective, open label study carried out at 6 Italian endocrinological centers. The effects of 6 months of SR lanreotide, given at first every 14 days at a dosage of 30 mg, im, were recorded. In some patients (33%), drug dosage was adjusted by increasing the dose (to 60 mg, im) and/or shortening the time interval (every 10 days) of SR lanreotide administration. Fifty patients completed the 6-month period of therapy; 2 subjects dropped out because of adverse events, and 5 dropped out because of ineffectiveness after changes in drug administration. The first SR lanreotide injection produced more than 50% suppression of GH levels from the basal value in 93% of patients. Thirteen days later, baseline GH levels were reduced by over 50% in 25% of patients. Mean GH values were normalized in 85% of patients after 6 months, whereas insulin-like growth factor I (IGF-I) levels were normalized in 38% of patients. No correlation was found between pretreatment GH levels and GH response to SR lanreotide or between changes in GH and IGF-I during therapy. During treatment, there was a significant reduction in the percentage of patients complaining of joint pain, hyperhydrosis, and paresthesias. Changes in soft tissue swelling were documented by significant decreases in finger measurements. Diarrhea and abdominal pain were the most frequent side-effects when therapy was started; these progressively decreased. After the first month of therapy, moderate, mild, and no side-effects were reported by 3%, 40%, and 53% of patients. A nonsignificant increase occurred in asymptomatic gallstones and amylase levels. Minimal changes were noted in carbohydrate tolerance, consisting of a slight increase in glycosylated hemoglobin, a rise in glucose and a decrease in pre- and postprandial insulin levels. No effects on PRL, free cortisol, TSH, or free thyroid hormone levels were noted. No significant change in the percentage of visual field abnormalities was noted. Decreases in pituitary tumor size occurred in 3 of 17 patients reevaluated after 6 months of therapy. The 6-month period of SR lanreotide therapy was compared, on an anamnestic basis, with a 6-month or longer period of sc octreotide therapy (median, 300 micrograms/day) in 34 patients. There were no differences in effectiveness or tolerability between the 2 somatostatin analogs. These data indicate that SR lanreotide at a dose of 30 mg, im, every 14 days is an effective treatment in most unselected acromegalic patients. When administered to a group of poorly responsive patients, an increase in drug dose (60 mg im) and/or a shortening of the drug interval (10 days) seem to improve the GH/IGF-I response. Tolerability to SR lanreotide therapy is high. The use of a new sustained release formulation of somatostatin analog is clearly advantageous in improving patient compliance with medical treatment for acromegaly.
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PMID:Effectiveness and tolerability of slow release lanreotide treatment in active acromegaly: six-month report on an Italian multicenter study. Italian Multicenter Slow Release Lanreotide Study Group. 895 72

Octreotide (OCT) administration provides a biochemical cure in most acromegalic patients. This drug, however, causes several side effects and is very expensive. Acute testing has been reported to predict chronic responsiveness to OCT administration. The aim of this retrospective study was to evaluate which test, if any, among acute testing, short-term (1 month) administration, and 111In-pentetreotide (111In-DTPA-Phe-D-OCT) scintigraphy, is best in predicting response to long-term OCT treatment. Sixty-eight patients with active acromegaly were studied. An acute test (100 micrograms sc OCT) was performed as usual: a GH decrease greater than or equal to 50% of baseline was considered a positive response. GH and insulin-like growth factor I (IGF-I) were then assayed after 1 month (300 micrograms daily) and 3 months (150-600 micrograms daily) of OCT administration. GH was considered normalized when decreased less than or equal to 5 micrograms/L. Twenty-six of 68 patients were subjected to 111In-pentetreotide scintigraphy. Linear correlation analysis of the results was performed. Sensitivity, specificity, and positive and negative predictive values of the three tests were also calculated. Thirty-eight of 68 patients (56%) responded to the acute test. Among these 38 patients, 20 experienced normalization of GH and IGF-I levels during long-term therapy, as did 8 patients who did not respond to the acute test. No significant correlation was found between GH percent decrease during acute testing and long-term therapy (r = 0.11). Seven patients who responded to the acute test and 2 who did not respond had adenoma shrinkage during therapy. Conversely, GH and IGF-I decrease after short-term treatment significantly correlated with long-term treatment (r = 0.76 and 0.64, P < 0.01). Of the 26 patients subjected to 111In-pentetreotide scintigraphy, 13 had significant tracer uptake: normalization of GH and IGF-I was obtained in 8 patients. A significant correlation was found between tracer uptake and GH/IGF-I inhibition after 3 months of therapy (r = 0.6; P < 0.05). In the whole population, the positive predictive value of acute testing, short-term OCT administration, and 111In-penetreotide scintigraphy was 53%, 70%, and 73%, respectively, when the GH normalization (< 5 micrograms/L) after 3 months of therapy was considered. Moreover, 111-In-pentetreotide scintigraphy had the highest specificity (100% in patients with baseline GH values below 50 micrograms/L) compared with that of acute testing and short-term OCT administration. The acute test cannot be considered as a valuable index to identify patients' responsiveness to long-term OCT therapy, but it can be useful to test tolerability. By contrast, 1 month of OCT administration or the in vivo imaging of somatostatin receptors by 111-In-pentetreotide might better indicate the patients who might effectively benefit from this treatment.
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PMID:Prediction of efficacy of octreotide therapy in patients with acromegaly. 896 77

Somatostatin analogs are an alternative treatment to pituitary surgery and radiotherapy in acromegalic patients. Recently, a depot long-lasting formulation of slow release (SR) lanreotide has been shown to be effective in the short-term control of GH hypersecretion in acromegalic patients. We report the long-term follow-up of a cohort of 22 acromegalic patients treated with SR lanreotide during 1-3 yr. Thirteen females and 9 males, age 51 +/- 3 yr, presented with macroadenomas (n = 12), microadenomas (n = 8), or empty sella (n = 2). Seven patients previously had undergone a partial surgical removal of their adenomas, and 21 of them had mean plasma GH levels less than 5 micrograms/L during a previous octreotide treatment. According to GH values recorded after 3 months of twice monthly 30 mg SR lanreotide im injection, SR lanreotide was administered every 14 days (n = 13) or every 10 days (n = 9). At the 6-month visit, mean GH values were 5 micrograms/L or less in 68% and 2.5 micrograms/L or less in 27% of patients, and these results remained unchanged during the 1-3 yr follow-up period. During SR lanreotide treatment, the mean insulin-like growth factor I (IGF-I) concentrations remained in the normal range in 63% of patients. No escape from the treatment occurred in any of the cases. A significant decrease of the pituitary tumor volume was observed in 3 (13%) patients. The main side effect consisted of minor digestive problems during 48 h after each injection and was reported by 13 patients. Biannual gallbladder echographies revealed the occurrence of gallstones in 4 (18%) patients. In conclusion, these data confirm the efficacy and the tolerance of the long-term SR lanreotide administration (30 mg im every 10-14 days) in the control of acromegaly.
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PMID:Three year follow-up of acromegalic patients treated with intramuscular slow-release lanreotide. 898 24

The ontogeny of endocrine cells and nerve fibers containing immunoreactivities for 12 regulatory peptides and serotonin was studied in the digestive tract of a flatfish, the turbot (Scophthalmus maximus), using antisera specific for mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR) endocrine cells were detected from day 5 to day 10 in stomach and intestine I. Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine I. In contrast to the islet cells, they reacted with antisera against mammalian (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti-mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present in the gastro-entero-pancreatic system and the enteric nervous system. Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP-immunoreactivities coexisted throughout development. In entero-endocrine cells, NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They seemed to contain none of the other peptides. Their number and distribution exhibited great interindividual differences. Vasoactive intestinal polypeptide (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP-IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)-IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day 17. The first serotonin (SER)-IR cells were observed in the stomach anlage around day 10 and SER-IR nerve fibers at day 15 throughout the gastro-intestinal tract. Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells were identified in the stomach anlage and intestine I around day 8 and contained NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several developmental phases can be distinguished: (1) at the onset of exogenous feeding only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a differentiated entero-endocrine system establishes during the early phase of exogenous feeding; (3) before the final differentiation of stomach and gut GAS/CCK-IR cell appear; (4) after metamorphosis most of the different types of regulatory peptide-containing nerve fibers develop, probably setting up the fine regulation of gastro-intestinal blood flow and motility.
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PMID:An immunohistochemical analysis of the ontogeny, distribution and coexistence of 12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the digestive tract of the turbot, Scophthalmus maximus (Teleostei). 900 19

Medical therapy is frequently needed to normalize growth hormone/insulin-like growth factor I secretion in acromegaly. The aim of this study was to determine the long-term effects of the slow-release (SR) somatostatin analogue lanreotide in 57 acromegalic patients. SR lanreotide (30 mg) was given every 14 days for 12 months. In 33% of patients, the drug dosage was raised to 60 mg and/or the time interval was shortened to 10 days. Two months of clinical evaluation followed drug discontinuation in 47 out of 48 (84%) patients who completed the 12-month period. A drug-related decrease in GH/IGF-I levels was observed. Basal GH/IGF-I levels were significantly (P < 0.001) reduced at 12 months, IGF-I was normalized in 35% of patients and GH levels were < 5 micrograms L-1 in 54%. There was a clinical improvement in patients complaining of joint pain, rachialgias, headache, digital paraesthesias and hyperhidrosis. Soft-tissue changes were documented by significant (P < 0.001) decreases in finger size. In 52 (91%) patients without overt diabetes, a slight but significant increase in integrated glycaemia (P < 0.001) was noted, while integrated insulin levels were reduced (P < 0.001). Of 33 (58%) patients with normal basal ultrasound examination of the gall bladder, three (9%) had developed asymptomatic gall stones or biliary sludge after 12 months. Adverse events were generally mild. They frequently (52%) occurred after the first SR lanreotide administration; only 28% were recurrent and 20% appeared for the first time during therapy. SR lanreotide is an effective treatment in most unselected acromegalic patients. Tolerance towards the drug is high. Subjective benefits seem to override the simple biochemical control of the disease. Glucose homeostasis more than the incidence of gall stones seems to require monitoring on therapy. SR lanreotide is clearly advantageous in improving patient compliance with medical treatment for acromegaly.
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PMID:Clinical results of long-term slow-release lanreotide treatment of acromegaly. 913 75

We evaluated growth hormone (GH) and insulin-like growth factor I (IGF-I) response to moderate submaximal acute short-term physical exercise under basal conditions and after the administration of octreotide, a somatostatin analogue (SA), in a double-blind, counter-balanced experimental protocol. Seven untrained male volunteers performed two identical exercise tests, each on a treadmill (2.5% slope) for 30 minutes (min) at 60% of VO2max. Before starting the exercise test all the subjects received a single administration of placebo or octreotide and vice versa at two different sessions. Plasma GH, IGF-I and lactate assays were evaluated before starting, during, at the end and in the recovery phase. In the placebo-treated group GH rose significantly both during exercise and recovery whereas no significant modifications in IGF-I levels were observed. SA administration inhibited the exercise-dependent GH secretion, which showed a small rise only during exercise and returned to basal levels during recovery. In the same group, IGF-I decreased significantly after exercise compared to basal values. The results suggest that 1) in our experimental conditions acute physical exercise at aerobic threshold does not modify IGF-I concentration 2) SA is able to inhibit the exercise-dependent GH secretion and to decrease post-exercise IGF-I concentration.
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PMID:Growth hormone and insulin-like growth factor I responses to moderate submaximal acute physical exercise in man: effects of octreotide, a somatostatin analogue, administration. 923 41

In pregnancy, the human placenta GH acts as a growth-promoting hormone and appears to be the main stimulator of insulin-like growth factor I (IGF-I) secretion. In a woman with a TSH-secreting macroadenoma, successful treatment with the somatostatin analog octreotide was conducted during the first month and the second half of pregnancy without side-effects on placental and fetal development. As observed in normal pregnancy, both serum placental GH and IGF-I levels increased throughout pregnancy and dropped sharply after delivery. In placental membranes from both treated and healthy untreated patients, we demonstrated the presence of high affinity binding sites for somatostatin-14 (Kd, 4.6 and 5.3 nmol/L; binding capacity, 1.53 and 1.35 pmol/mg protein, respectively). These receptors displayed low affinity for octreotide (IC50, 1.2-2 mumol/L), suggesting the presence of SST1 and/or SST4 receptors. We found that messenger ribonucleic acids of these two subtypes were expressed in both human placental tissue and purified human cytotrophoblast cells. Finally, the SST1-selective analog, des-AA1,2,5[D-Trp8,IAmp9]S-14 had low affinity for placental somatostatin receptors. These results argue in favor of the presence of the SST4 subtype in human placenta. At the doses administered, octreotide did not bind to placental somatostatin receptors. Our results may explain the absence of changes in both human placental GH and IGF-I concentrations that we observed during octreotide treatment.
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PMID:Expression of somatostatin receptor SST4 in human placenta and absence of octreotide effect on human placental growth hormone concentration during pregnancy. 936 May 39

The synthetic hexapeptide GH-releasing peptide (GHRP) stimulates a dose-dependent release of GH in humans in vivo and in animals both in vitro and in vivo via a specific receptor in the hypothalamus and pituitary. To determine the action of GHRP in the human fetal pituitary, reverse transcription-PCR was performed, and GHRP receptor messenger ribonucleic acid expression was detected in fetal pituitaries of 18- and 31-week gestation. Therefore, primary human fetal pituitary cultures (second and third trimesters) were treated with GHRP-6. GHRP-6 dose-dependently increased GH secretion from human fetal pituitary cultures by up to 80% (P < 0.001; maximal effect achieved with 100 nmol/L), whereas GHRH (10 nmol/L) stimulated GH by up to 120% (P < 0.001). However, GHRP together with GHRH was additive (up to 2.8-fold GH induction) with no evidence of further positive synergy. In contrast to GHRH, GHRP-6 did not alter human ACTH and PRL levels. A treatment time of 2 h was required for maximal GH stimulation. GHRP-6 reversed suppressed GH levels in cultures cotreated with either insulin-like growth factor I (P < 0.0001) or somatostatin (P < 0.05). GHRP-6 and GHRP-2 (100 nmol/L) had similar effects in stimulating human GH release. These results show a direct in vitro action of GHRP on human pituitary cells. GHRP is less potent than GHRH in directly releasing GH from human somatotrophs, and only additive effects of these two peptides occur at the level of the human fetal pituitary.
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PMID:Human fetal pituitary expresses functional growth hormone-releasing peptide receptors. 962 66

Male- and female-specific modes of episodic growth hormone (GH) release are presumptively imposed by sex steroid hormones, and, although typically evident visually, are vividly distinguished quantitatively via a regularity statistic, approximate entropy (ApEn), in both the rat and human. GH secretory patterns may determine GH-stimulated growth and specific hepatic and muscle gene expression in the rat. Consequently, it is important to discern mechanisms that underlie their regulation. Here we have examined the impact of prepubertal gonadal suppression (at 4 wk of age) via surgical or pharmacological [gonadotropin-releasing hormone (GnRH) agonist] intervention on the regularity (ApEn) of GH release in male and female rats (at 10-11 wk of age) sampled at 10-min intervals for 10 h (n = 60 points) during a lights-out (dark) period. We observed a graded hierarchy of mean disorderliness of GH release that was quantifiable by ApEn measures, with maximal to minimal disorderliness in the following rank order: intact female, GnRH agonist-treated female, ovariectomized female, orchidectomized male, GnRH agonist-treated male, and intact male. These observations suggest a continuum of sex steroid actions on the regularity of GH secretion and, by inference, on the interplay among GH-releasing hormone, somatostatin, and GH/insulin-like growth factor I negative feedback.
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PMID:Differential orderliness of the GH release process in castrate male and female rats. 948 2

The ontogeny of the classical islet hormones insulin (INS), glucagon (GLUC), somatostatin (SOM), and pancreatic polypeptide (PP) as well as insulin-like growth factor I (IGF-I) in the gastro-entero-pancreatic (GEP) system of Xenopus laevis (stages 41-66) was studied using double immunofluorescence and morphometric analysis. As early as stage 41, clustered INS-immunoreactive (-IR) and isolated GLUC-IR cells occurred in the pancreas. The first SOM-IR cells appeared at stage 43, followed by PP-IR cells at stage 46. About 79% of the PP immunoreactivity was confined to a subpopulation of the GLUC-IR cells. Both the GLUC/PP-IR cells and the PP-IR cells were located in a distinct area of the pancreas. The first islets occurred in premetamorphosis (around stage 50) and comprised mainly INS-IR and GLUC-IR cells. The majority of SOM-IR, PP-IR, and GLUC/PP-IR cells was dispersed. The numbers of hormone cells remained quite constant until the end of prometamorphosis (stage 58). Around stages 60-62, the islets were partly disintegrated and the numbers of islet cells slightly decreased. At stage 63, the cell number began to increase and reached the levels typical for the adult around stage 66. After metamorphic climax, the islets were reformed. In the gastrointestinal tract, transient INS-IR cells occurred prior to the adaptation of the gastrointestinal tract to feeding (stages 41-44) and during metamorphosis when there is remodeling of the gastrointestinal tract (stages 60-63). Therefore, INS released from the transient mucosal INS-IR cells may be involved in the temporary proliferation of mucosal epithelial cells. The first GLUC-IR and SOM-IR cells were seen at stage 41. PP-IR cells followed at stage 46. In contrast to the islets, GLUC-IR and PP-IR cells constituted different cell populations. Around stage 46, the first IGF-I immunoreactions appeared in the GEP-system. In pancreas, IGF-I immunoreactivity was found in the GLUC/PP-IR, cells (85-99%) but was absent from INS-IR, GLUC-IR, and SOM-IR cells. The IGF-I-IR gastro-entero-endocrine cells, however, seemed to contain none of the classical islet hormones.
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PMID:An immunohistochemical and morphometric analysis of insulin, insulin-like growth factor I, glucagon, somatostatin, and PP in the development of the gastro-entero-pancreatic system of Xenopus laevis. 957 Sep 39


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