Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide is a synthetic octapeptide somatostatin analogue which has higher potency and longer duration of action than the natural hormone. It is effective after subcutaneous administration and no rebound hypersecretion has been observed. Pharmacological effects of octreotide include inhibition of numerous hormones (growth hormone, TSH, insulin, glucagon and all gut hormones), of exocrine secretion (gastric acid, pancreatic enzyme), and of small-bowel absorption. This review deals with clinical application of octreotide in endocrine disorder. In patients with acromegaly octreotide treatment results in decrease of growth hormone (GH) and IGF-I together with tumour shrinkage and clinical improvement. Although variability in response to treatment is obvious for majority of patients the most effective dose is 100 mcg three times daily subcutaneously. Normalization of GH levels could be achieved in more than 50% of treated patients. It has also been shown that octreotide could be effective in TSH secreting pituitary adenoma, ACTH secreting adenoma as well as in non-secretory pituitary tumours. A marked biochemical and clinical responses together with longer survival have been reported in most of the patients with gastroenteropancreatic (GEP) tumours. Patients who benefit the most from octreotide therapy are those with carcionid syndrome (successful control of diarrhoea, flushing episodes and wheezing) and VIPomas (control of diarrhoea). In patients with insulin-dependent diabetes mellitus (IDDM) octreotide suppresses GH levels, postprandial blood glucose increases with resultant decrease in daily insulin requirements. In women with polycystic ovary syndrome (PCOS) octreotide has inhibitory effect on serum LH and ovarian androgens. This could have beneficial effect on ovulatory performance in women with PCOS.
 ...
PMID:[Clinical use of octreotide (Sandostatin) in endocrinology]. 799 11

Availability of recombinant growth hormone (GH) and development of long-acting formulations of this material will undoubtedly lead to widespread use of GH in animal industry and in medicine. GH can act, directly or indirectly, on multiple targets, but its influence on the reproductive system and on the hormonal control of reproduction is poorly understood. Overexpression of GH genes in transgenic animals provides a unique opportunity to study the effects of long-term GH excess. Transgenic mice overexpressing bovine, ovine, or rat GH (hormones with actions closely resembling, if not identical to, those of endogenous [mouse] GH), exhibit enhancement of growth, increased adult body size, and reduced life-span as well as a number of endocrine and reproductive abnormalities. Ectopic overexpression of bovine GH (bGH) driven by metallothionein or phosphoenolpyruvate carboxykinase promoters is associated with altered activity of hypothalamic neurons which produce somatostatin, loss of adenohypophyseal GH releasing hormone (GHRH) receptors, and suppression of endogenous (mouse) GH release. Elevation of plasma levels of GH (primarily bGH) and insulin-like growth factor (IGF-I) in these transgenic mice leads to increases in the number of hepatic GH and prolactin (PRL) receptors, in the serum levels of GH-binding protein (GHBP), in the percent of GHBP complexed with GH, and in the circulating insulin levels. In addition, plasma adrenocorticotropic hormone (ACTH) and corticosterone levels are elevated. Plasma levels of luteinizing hormone (LH), as well as its synthesis and release, are not consistently affected, but follicle-stimulating hormone (FSH) levels are suppressed, apparently due to pre- and post-translational effects. Pituitary lactotrophs exhibit characteristics of chronic enhancement of secretory activity, and plasma PRL levels are elevated. Prolactin responses to mating or to pharmacological blockade of dopamine synthesis are abnormal. Reproductive life span and efficiency are reduced in both sexes, with the severity and frequency of reproductive deficits being related to plasma bGH levels. Most transgenic females expressing high levels of bGH are sterile due to luteal failure. Overexpression of human GH which, in the mouse, interacts with both GH and PRL receptors leads to additional endocrine and reproductive abnormalities including stimulation of LH beta mRNA levels and LH secretion, loss of responsiveness to testosterone feedback, overstimulation of mammary glands, enhanced mammary tumorigenesis, and hypertrophy of accessory reproductive glands in males.
 ...
PMID:Neuroendocrine and reproductive consequences of overexpression of growth hormone in transgenic mice. 807 44

Mitogenic responsivity of many neoplasms to IGF-I has been detected in a variety of in vivo and in vitro experimental systems. This has led to the proposal that pharmacological reduction of IGF-I bioactivity might represent a novel non-cytotoxic palliative therapy. We recently reported that tamoxifen, a commonly used antiestrogen antineoplastic agent, significantly suppresses IGF-I gene expression and serum IGF-I levels. We report here that the somatostatin analogue octreotide, previously demonstrated to reduce acromegalic levels of IGF-I towards normal, decreased serum IGF-I to 70 +/- 4% (mean +/- SD) of control values and hepatic IGF-I expression to 65 +/- 10% of control values in a short-term non-acromegalic rat model. Tamoxifen reduced serum IGF-I to 74 +/- 12% of control values and hepatic IGF-I expression to 46 +/- 9% of control values in this model, but the combination of octreotide and tamoxifen reduced serum IGF-I concentration to 49 +/- 10% of control values and hepatic IGF-I gene expression to 12 +/- 9% of control values. The levels of serum IGF-I and hepatic IGF-I gene expression were significantly less in animals treated with the combination of octreotide and tamoxifen than in animals treated with either agent alone (p < .01). This combination represents a novel pharmacological strategy for suppressing IGF-I gene expression that may be relevant to the design of clinical trials.
 ...
PMID:Enhancement of tamoxifen-induced suppression of insulin-like growth factor I gene expression and serum level by a somatostatin analogue. 807 63

Growth hormone (GH) secretion is markedly blunted in obesity. Reportedly, genetically obese Zucker rats show a reduced GH secretion due to an impaired function of hypothalamic neurons producing the GH-releasing hormone (GHRH). The aim of this work was: (1) to compare the in vitro GH responsiveness to GHRH in genetically obese female versus male Zucker rats and, (2) to evaluate the function of hypothalamic GHRH and somatostatin and of pituitary receptors for these neurohormones as assessed by the effectiveness of GHRH and somatostatin on adenylate cyclase (AC) activity. Baseline GH secretion of pituitaries obtained from male and female obese rats was not different and similar to that present in lean counterparts. Stimulation with 10(-7) M GHRH elicited a significantly lower GH secretion from the pituitaries of obese male rats but induced a similar GH secretion from the pituitaries of lean and obese female rats. In these pituitaries, GH concentration was similar in obese versus lean male and female rats [corrected]. A sex-related difference was also evidenced when plasma concentrations of somatomedin C (IGF-I) were evaluated. Obese male rats had lower IGF-I concentrations than lean counterparts, while this was not the case for obese versus lean female rats. Evaluation of AC activity following GHRH disclosed a lower activation in obese than in lean male rats, whereas in the females the enzyme activation was higher in obese than in lean animals. Conversely, the inhibitory effect of somatostatin on forskolin-stimulated AC was similar in pituitary membranes of obese and lean rats of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Growth hormone secretion is differently affected in genetically obese male and female rats. 810 99

There is evidence that GH secretion is reduced in normal elderly subjects as well as in patients with Alzheimer's disease (AD). To clarify the mechanisms underlying this GH hyposecretory state in 14 elderly subjects (age 65-75 years) and 15 AD patients (age 61-78 years), we studied the effects of both pyridostigmine (PD, 120 mg orally), a cholinesterase inhibitor, and arginine (ARG, 0.5 g/kg i.v.), two substances likely acting via inhibition of hypothalamic somatostatin, on GH response to GHRH (1 microgram/kg i.v.). The GH response to PD alone was also studied. Twenty-two young healthy volunteers were studied as control group. Basal GH levels were similar in young, elderly and AD subjects (0.7 +/- 0.2, 0.8 +/- 0.2 and 0.9 +/- 0.2 microgram/l). IGF-I levels were lower (p < 0.005) in elderly (73.9 +/- 8.2 microgram/l) and in AD subjects (108.0 +/- 5.9 micrograms/l) than in young subjects (288.7 +/- 22.1 micrograms/l); however, they were higher (p < 0.01) in AD patients than in the elderly subjects. The PD-induced GH release did not significantly differ in young, elderly and AD subjects while the GH responses to GHRH in the elderly (AUC: 297.9 +/- 49.2 micrograms/l) and in AD subjects (437.6 +/- 93.5 micrograms/l/h) were lower (p < 0.01) than in young subjects (658.6 +/- 100.1 micrograms/l/h). PD potentiated the GH response to GHRH both in elderly and in AD subjects (901.7 +/- 222.4 and 1,070.3 +/- 207.2 micrograms/l/h, p < 0.005) but these responses were lower (p < 0.0001) than those recorded in young subjects (2,041.1 +/- 245.6 micrograms/l/h).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Growth hormone secretion in Alzheimer's disease: studies with growth hormone-releasing hormone alone and combined with pyridostigmine or arginine. 813 94

Peptides such as somatostatin (SS14), epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and insulin-like growth factors (IGF-I and IGF-II) are present in breast milk from various species, and their significance in the developing gastrointestinal tract has been suggested. Our recent studies have indicated that rat milk soluble fraction (RMSF) protects SS14 in the gastrointestinal lumen by inhibiting in vitro the luminal peptidolysis. In the present studies, we have shown that RMSF inhibited in vitro degradation by midjejunal luminal flushings of suckling rats of 125I-labeled somatostatin 14[Tyr11], EGF, TGF alpha, IGF-I and IGF-II, as well as trypsin activity in vitro against benzoyl-L-arginyl-p-nitroanilide. The inhibitory factors present in the RMSF were further fractionated by gel filtration on Sephadex G100, ion-exchange chromatography on DEAE-Sephadex, and fast protein liquid chromatography (FPLC). Gel filtration of Sephadex G100 separated RMSF into three peaks of proteins: G1, G2, and G3; peptidase inhibitor activities were present exclusively in G1. Ion-exchange chromatography on DEAE-Sephadex column resolved peptidase inhibitory activity (G1) into three different peaks, D1, D2, and D3, eluted at sodium chloride concentrations of 0.05 M, 0.1 M, and 0.2 M, respectively. Further purification of D2 by FPLC resulted in a fraction rich in peptidase inhibitory activity, which was essentially free of trypsin inhibitory activity. Results indicate the presence of at least three peptidase inhibitors in rat milk, which may play a role in the protection of milk-borne peptides in the gastrointestinal lumen.
 ...
PMID:Presence of multiple forms of peptidase inhibitors in rat milk. 814 98

Octreotide, as well as endogenous somatostatin, inhibits GH and TSH secretion. The drug is employed in the medical therapy of acromegaly. We studied the effects of a long-term (1-120 months; median 12 months) therapy with octreotide (300 micrograms/day) given in 3-times intermittent s.c. administration or in pulsatile s.c. (25 micrograms/120 min) way, upon the pituitary-thyroid axis. Thirteen patients (11 with normal thyroid function, 1 with secondary hypothyroidism, 1 with toxic goiter) with active acromegaly were studied. In the euthyroid patients no significative variations in both TSH levels and thyroid hormones were found during octreotide therapy. In the non-euthyroid patients octreotide did not induce changes in the dosages of drugs acting to thyroid function. The 24-hour IC-TSH levels did not show any variation during octreotide. TSH response to TRH was reduced (P < 0.05) during octreotide therapy. No correlation among TSH, IGF-I and GH levels was observed. Long-term treatment of acromegaly with octreotide reduces TSH response to TRH but do not interfere with both 24-hour IC-TSH levels and thyroid function.
 ...
PMID:[Behavior of the pituitary-thyroid axis in acromegalic subjects during prolonged intermittent and pulsatile treatment with octreotide]. 818 83

The purpose of this study was to determine whether the long-acting somatostatin analog SMS 201-995 (octreotide) shrinks growth hormone (GH)-secreting adenomas and improves the results of subsequent transsphenoidal surgery. Ten previously untreated active acromegalic patients (nine women and one man) with invasive tumors were treated with SMS 201-995 (100 micrograms subcutaneously every 8 hours) for 6 weeks prior to transsphenoidal surgery. The clinical activity, mean GH secretion, insulin-like growth factor (IGF)-I concentration, and tumor volume were measured under basal conditions and on Days 14, 28, and 42 of treatment. The SMS 201-995 improved the symptoms of acromegaly in all patients. Mean levels of both GH and IGF-I (+/- standard deviation) were significantly decreased by Day 14 (from 92.9 +/- 30.5 to 44.9 +/- 20.3 micrograms/liter and from 10.6 +/- 7.4 to 5.9 +/- 2.6 U/ml, respectively), after which there were only slight further decreases. Six (60%) of the 10 patients experienced tumor shrinkage ranging from 9% to 78% (mean 30%). When it occurred, tumor shrinkage was significant by Day 14 (7.9 +/- 6.3 to 6.5 +/- 5.1 cu cm) and no further shrinkage was achieved by longer administration. Transsphenoidal surgery reduced postoperative GH levels to less than 2 micrograms/liter and IGF-I to less than 1.5 U/ml in six patients (60%). This percentage of cure is higher than expected from the literature and the authors' previous experience. However, an investigation of the influence of this drug on several parameters, such as reduction of tumor size or GH and IGF-I concentrations, has failed to prove any relationship. Only pretreatment size of the tumor was of predictive value with respect to the surgical outcome.
 ...
PMID:Treatment of invasive growth hormone pituitary adenomas with long-acting somatostatin analog SMS 201-995 before transsphenoidal surgery. 820 9

Spontaneous GH secretion as well as GH response to several stimuli including GHRH have been shown to be reduced in obesity. To clarify the pathogenesis underlying these alterations, in six obese patients (3 males and 3 females, age 20-44 yrs, BMI = 42.1 +/- 2.2) on unrestricted diet we studied the effect of 8 day GHRH pretreatment (1 micrograms/kg iv each day) on the acute somatotropic response to the neurohormone administered both alone and combined with arginine (ARG, 0.5 g/kg iv infused from 0 to 30 min) which likely inhibits the release of hypothalamic somatostatin. Before treatment the GH response to GHRH (AUC: 231.9 +/- 106.4 micrograms/l/h) was potentiated (p < 0.001) by ARG (932.6 +/- 166.2 micrograms/l/h). However, the GH responses to the neurohormone both alone and combined with ARG were lower (p < 0.02 and 0.002, respectively) than in normals (712.4 +/- 111.6 and 2608.3 +/- 453.2 micrograms/l/h, respectively). After repetitive GHRH administration, in obese subjects baseline GH and IGF-I levels were unchanged. Also the GH responses to GHRH both alone (217.3 +/- 68.1 micrograms/l/h) and combined with ARG (756.3 +/- 202.9 micrograms/l/h) were not modified. In conclusion, our data demonstrate the failure of GHRH pretreatment to improve the somatotrope hyporesponsiveness to GHRH both alone and combined with ARG suggesting the existence of a somatotropic defect in obesity.
 ...
PMID:Repetitive GHRH administration fails to increase the response to GHRH in obese subjects. Evidence for a somatotrope defect in obesity? 834 45

Pituitary tumours result in hypersecretion of different hormones which can be used in diagnosis. Prolactinomas can be diagnosed by measurement of prolactin serum concentration. Prolactin concentrations of > 150 to 200 micrograms/l are invariably due to macroprolactinoma. Lower levels may indicate microprolactinoma or a peripituitary tumour. Computed tomography scans visualize (micro)prolactinomas of 3 mm. Diagnosis of acromegaly is now based on measurement of serum IGF-I concentration. IGF-I levels correlate with the old test which measured insufficient suppression of GH levels to < 2 micrograms/l in response to oral glucose load. Most endocrine tumours have somatostatin receptors, allowing visualization with radiolabelled somatostatin analogues. 111In-diethylenetriaminopentaacetic acid-octreotide allows normal pituitary and somatostatin positive tumours to be visualized. A positive scan is predictive of good response to octreotide therapy. Cushing's syndrome is diagnosed by ecchymoses, myopathy, hypertension, and by measurement of the overnight 1 mg dexamethasone suppression test, urine cortisol levels and the diurnal cortisol rhythm. Clinically nonfunctioning macroadenomas in post-menopausal women often do not immunostain for gonadotropins. Serum gonadotropin levels are not elevated, although they do release gonadotropins or subunits in vitro. Diagnosis is assisted by TRH administration which increases serum gonadotropins or subunits, especially LH-beta.
 ...
PMID:Current tools in the diagnosis of pituitary tumours. 837 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>