Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 available somatostatin analogs for subcutaneous administration lower growth hormone (GH) levels in more than 90% of patients and Insulin-like growth factor-I (IGF-I) levels in up to 60%. They are also capable of reducing tumor size in up to 50%. Recently long-acting somatostatin analogs were introduced. The use of these application forms can result in normalization of IGF-1 in 60% of patients after 1 year and in 75% after 3 years. The development of selective analogs for the somatostatin receptor subtype-5 potentially will enhance the potency and the spectrum of the medical treatment of acromegaly with somatostatin analogs. The new generation of dopaminergic drugs also form a potentially effective and well tolerated therapy that should be considered in the management of those acromegalic patients, which have relative low serum IGF-I concentrations, along with high serum prolactine levels. Finally, growth hormone receptor (GHR) antagonists are under development for the use in humans. Preliminary results look promising, when biochemical parameters are concerned. Interim analysis of a phase 3 study with B2036-PEG in 38 patients does show that normalization of IGF-I concentrations is reached in at least 92% of the treated patients.
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PMID:New medical treatment for acromegaly. 1108 Nov 77

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin LAR on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans. Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin LAR and eight patients underwent transsphenoidal surgery. Serum concentrations of leptin, GH, IGF-1 and insulin were measured before and after treatment. Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2.79 microg/l (2.60) vs. 4.41 microg/l (5.07); median (inter-quartile range); P < 0.01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0.46, P < 0.05) but not in the acromegalic patients before treatment (r = 0.32, ns). In the group of patients treated with Sandostatin LAR, a marked reduction in GH and IGF-1 was achieved by week 8 and GH and IGF-1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2.99 microg/l (2.60) vs. 4.21 microg/l (3.84), P < 0.05]. Leptin levels also significantly increased after transsphenoidal surgery [3.05 microg/l (5.73) vs. 5.19 microg/l (4.93), P < 0.05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin LAR (r = 0.62, P < 0.05) and after surgery (r = 0.81, P < 0.05). Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin LAR or transsphenoidal surgery led to an increase in leptin concentrations.
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PMID:Effect of Sandostatin LAR on serum leptin levels in patients with acromegaly. 1116 23

Estrogen is the proximate sex steroid sustaining GH secretion throughout the human life span in both sexes. However, very little is known about the specific neuroendocrine mechanisms by which estrogen activates and maintains GH secretion in the young or aging human. The identification of somatostatin in 1973 as a key negative peptidyl regulator of the GH axis and the discovery of GH-releasing hormone (GHRH) in 1982 as a dominant feedforward agonist of GH secretion provided an initial basic science foundation for exploring sex-steroid control of the GH-IGF-1 axis. Although GH-releasing peptides (GHRPs) were first recognized in 1977-1981, subsequent cloning of hypothalamopituitary receptors transducing potent secretagogue actions of GHRPs in 1996 and of an endogenous ligand for this effector pathway in 1999 now extend the framework for examining the mechanisms of estrogen-driven GH secretion in aging. Herein, we review several novel and multifaceted interactions in postmenopausal women between estrogen and GHRP-2. We combine these observations into a simplified construct of GH-axis neuroregulation comprising the somatostatin, GHRH, and GHRP effector pathways, as well as GH and IGF-1 autofeedback. We suggest the thesis that estrogen controls the interfaces among these pivotal regulatory peptides in hyposomatotropic postmenopausal individuals.
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PMID:Interactive regulation of postmenopausal growth hormone insulin-like growth factor axis by estrogen and growth hormone-releasing peptide-2. 1132 1

One of the most active topics in the growth hormone-IGF-1 field is that of the so-called growth hormone secretagogues (GHS). At a time when the isolation of GHRH had not occurred, the GHS were developed as artificial tools to release GH. The interest in these groups of compounds was rekindled when it was realized that they were not surrogates of GHRH nor were they acting through the modulation of the release of either GHRH or somatostatin. With the subsequent cloning of the specific receptor of GHS, and today of the natural ligand for that receptor, named ghrelin, it soon become clear that GHS and the GHS-receptor were part of a new physiological system involved in GH regulation. The dual control of GH secretion became a trinity. GHS releases GH when administered by any route--oral, iv, sc, and even transdermally-with a surprising potency and reproductivity. In addition, GHS when administered together with GHRH exert a synergistic action on GH secretion and that combined administration is the most potent GH releaser to date. Clinical studies have demonstrated that the GHS-GHRH administration may be considered the new "gold standard" test of GH reserve in humans, as the GH secretion so elicited is not altered by gender, adiposity, or age. The combined administration of GHRH plus GHS is able to discriminate between healthy subjects and patients with adult GH deficiency, suggesting a considerable utility in the clinical setting.
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PMID:Growth hormone secretagogues as diagnostic tools in disease states. 1132 8

The aim of this study was to determine whether growth hormone treatment reduces injury to the intestinal mucosa induced by methotrexate (MTX). Wistar rats with intestinal injury induced by methotrexate were treated with daily growth hormone, beginning 3 days before MTX treatment until 3 or 4 days after MTX administration. The rats were killed at 3 or 7 days post-MTX administration. The rats were fed with either a normoproteic diet or a hyperproteic diet. Body weight, mortality, bacterial translocation, intestinal morphometry, proliferation and apoptosis and blood somatostatin and IGF-1 were determined. Combined administration of growth hormone and a hyperproteic diet reduces MTX-induced mortality. This effect was accompanied by increased cell proliferation and decreased apoptosis within the crypt. Morphometric data showed complete recovery of the mucosa by day 7 post-MTX administration. These results indicate a synergistic protective action of growth hormone combined with a hyperproteic diet to MTX-induced injury.
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PMID:Effects of growth hormone plus a hyperproteic diet on methotrexate-induced injury in rat intestines. 1166 34

Somatostatin (SRIF) exerts inhibitory effects on virtually all endocrine and exocrine secretions. Five distinct SRIF receptor subtypes (sst 1-5) have been identified. In contrast to the other subtypes, very little is known about specific functions of sst4. We investigated structure and regulation of the human sst4 gene. A genomic clone containing the 5' region of the sst4 gene was isolated. 1.5 kb of the promoter was sequenced and putative transcription factor binding sites were identified. The transcription start site was located 88 nucleotides upstream of the translation start site. A -984 sst4 promoter directed significant levels of luciferase expression in GH4 rat pituitary cells, Skut-1B endometrium cells, and BEAS-2B human bronchial epithelial cells, whereas only low activity was detected in JEG3 chorion carcinoma cells or COS-7 monkey kidney cells. A minimal -209 promoter allowed cell specific expression, its activity in COS-7 cells is not enhanced by co-transfection of the pituitary-specific transcription factor Pit-1. An enhancer element was localized between nt -459 and -984. We did not find any regulation of the sst4 promoter region analyzed by SRIF, forskolin, TPA, IGF-1, EGF, T3, glucocorticoids or 17beta-estradiol. These studies identify the 5' region of the sst4 gene. Furthermore, specific activity of the promoter in various cell lines is demonstrated.
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PMID:Characterization of the human somatostatin receptor type 4 promoter. 1191 48

We review the evidence suggesting that hypothalamic growth hormone (GH)-releasing hormone (GHRH) stimulates sleep and growth hormone secretion simultaneously. GHRH injected into the cerebral ventricles, systemic circulation or the preoptic region enhances non-REM sleep (NREMS) in rats, rabbits and mice, and GHRH administered systemically promotes NREMS in humans. GHRH may also stimulate REMS but this effect is indirect and requires the presence of GH. Inhibition of endogenous GHRH (antibodies, antagonist, somatostatin, high doses of GH or IGF-1) suppresses both NREMS and GH secretion. Mutant rats and mice with deficiencies of GHRH signaling, and transgenic mice with decreased GHRH production sleep less than normal animals. Hypothalamic GHRH mRNA and GHRH content display diurnal variations and change in response to sleep deprivation. The NREMS-promoting activity of GHRH is independent of GH and is mediated by the preoptic region. It is suggested that promotion of NREMS and stimulation of GH are parallel outputs of hypothalamic GHRH through which anabolic activities in the body are are synchronized to periods of sleep.
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PMID:The somatotropic axis and sleep. 1192 22

Somatostatin and its stable analogues (octreotide, lanreotide and vapreotide) exert an antiproliferative effect on various normal and cancerous cells both in vitro and in vivo. This effect results from different mechanisms: an indirect effect by the inhibition of release of growth factors and trophic hormones (GH, IGF-1, insulin, gastrin, EGF), an inhibition of angiogenesis processes (endothelial cell proliferation, VEGF release, monocyte activity), an immunomodulatory effect (lymphocyte proliferation, interleukine or cytokine release, NK activity) and a direct effect on target cells. This direct antiproliferative effect is mediated through specific somatostatin receptors. Among them, sst(1), sst(2), sst(4) and sst(5) have been implicated in vitro in the G1-G0 cell cycle blockade, sst(3) and sst(2) mediating the apoptotic effect of somatostatin. In addition, sst(2) acts as an antioncogene in human pancreatic cancer cells. Coupling to membrane tyrosine phosphatases (SHP-1, SHP-2) is the main transduction pathway involved in the antiproliferative effect mediated by sst receptors. The dissociation observed clinically between a frequent antisecretory response and an inconstant antitumor effect after administration of somatostatin analogues may reflect an absence of expression or coupling of the receptor(s) involved in antiproliferative effect. Moreover, a desensitization or mutation of these receptors may also occur in tumors. All the potential mechanism involved should be elucidated in order to improve or better target the antitumor effect of somatostatin analogues clinically used.
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PMID:[Regulation of cell proliferation by somatostatin]. 1203 98

Lanreotide Autogel((R)) is a new long-acting aqueous preparation of lanreotide for the treatment of acromegaly, and is administered by deep sc injection from small-volume pre-filled syringes. The aim of this study was to evaluate the efficacy and safety of this new long-acting formulation in a large population of acromegalic patients previously responsive to im lanreotide 30mg (sustained release microparticle formulation). Lanreotide Autogel((R)) was administered by deep sc injection every 28 days to 107 patients (54 males, 53 females; mean age 54+/-1.2 years). All patients had been treated with lanreotide 30mg for at least 3 months before study entry, and had a mean GH level<10 ng/mL after at least four subsequent im injections every 14 days (48%), 10 days (32%) or 7 days (20%). Treatment was switched from lanreotide 30mg injected every 14, 10 or 7 days to lanreotide Autogel((R)) 60, 90 or 120mg, respectively, every 28 days. After three fixed-dose injections of lanreotide Autogel((R)), mean lanreotide levels were similar to those obtained at steady state with lanreotide 30mg. During lanreotide Autogel((R)) treatment, the control of acromegalic symptoms was comparable with that previously achieved during lanreotide 30mg treatment. After three injections of lanreotide Autogel((R)), mean values for GH (2.87+/-0.22ng/mL) and IGF-1 (317+/-15ng/mL) were comparable with those recorded at the end of lanreotide 30mg treatment (GH: 2.82 +/- 0.19ng/mL; IGF-1: 323+/-16ng/mL). GH<2.5ng/mL and age-sex-normalised IGF-1 was achieved in 33% and 39% of patients during lanreotide 30mg and lanreotide Autogel((R)) treatment, respectively. Diarrhoea, abdominal pain and nausea were reported by 38, 22 and 18% of patients during lanreotide 30mg treatment, and by 29, 17 and 9% of patients, respectively, during lanreotide Autogel((R)) treatment. In conclusion, this clinical study shows that lanreotide Autogel((R)) is at least as efficacious and well tolerated as lanreotide 30mg. This new long-acting lanreotide formulation, lanreotide Autogel((R)), which is administered from small-volume pre-filled syringes by deep sc injection, is therefore likely to improve the acceptability of medical treatment for patients requiring long-term somatostatin analogue therapy.
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PMID:[Somatuline(R) Autogel(R), a new formulation of lanreotide for the treatment of acromegalic patients]. 1203 99

Severe traumatic head injury has been recognized to be associated with hypothalamo-hypophyseal impairment and subsequent abnormalities in hormone secretion, which can contribute to a prolonged clinical course and to hampered recovery in many head-injured patients. Most of the data on the growth hormone/insulin-like growth factor -1 (GH/IGF-1) axis function have been obtained early after head injury, whereas GH secretory pattern has not been fully elucidated after patients had left the intensive care unit. We examined the activity of the GH/IGF-1 axis in 16 severely closed head-injured (CHI) patients (14 males; age range, 17 to 47 years; body mass index [BMI], 21.4 +/- 0.8 kg/m(2)) during the rehabilitation period at least 1 month after leaving the intensive care unit and in 12 sex-, age-, and weight-matched healthy controls. The severity of trauma was assessed by the Glasgow Coma Scale (GCS) score (8 or less), posttraumatic amnesia (PTA, more than 24 hours), and initial computed tomography (CT) scan. The clinical picture at time of the study was evaluated by the Rancho Los Amigos Scale of Cognitive Functioning (CFS) and the Functional Independence Measure (FIM). In all subjects, we evaluated basal levels of anterior pituitary hormones, IGF-1, insulin-like growth factor-binding protein (IGFBP)-3, and IGFBP-1, as well as the GH responses to intravenous (IV) infusion of growth hormone-releasing hormone (GHRH) alone, GHRH plus arginine (ARG), and the GH release evoked by somatostatin (SRIH) infusion withdrawal, which is related to endogenous GHRH tone. In all subjects, nutritional parameters and nitrogen balance were normal. Basal plasma concentrations of GH, IGF-1, IGFBP-3, and IGFBP-1 did not significantly differ between CHI patients and controls. The GH responses to GHRH and GHRH plus ARG did not significantly differ between CHI patients (GH peak, 10.7 +/- 3.0 microg/L; area under the curve [AUC], 5.9 +/- 1.5 microg/L. min; and GH peak, 34.7 +/- 6.1 microg/L; AUC, 20.25 +/- 3.3 microg/L. min, respectively) and normal subjects (GH peak at 30 minutes, 7.23 +/- 1.35 microg/L; AUC, 4.7 +/- 0.8 microg/L. min; and GH peak at 60 minutes, 41.0 +/- 5.1 microg/L; AUC, 24.3 +/- 1.7 microg/L. min, respectively). SRIH withdrawal resulted in an unequivocal increase in plasma GH concentrations both in CHI patients and in controls, without any significant difference between the 2 groups. A negative correlation was found between the GH response (deltaGH peak) to SRIH withdrawal and CFS (r = -.615, P <.005). In conclusion, our study indicates that patients receiving rehabilitation after leaving the intensive care unit for severe traumatic head injury have no significant changes of GH secretion with normal central regulation of the GH-IGF-1 axis.
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PMID:Evidence for integrity of the growth hormone/insulin-like growth factor-1 axis in patients with severe head trauma during rehabilitation. 1237 Aug 60


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