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)

The aim of this short review is to inform about the possibilities and limits of transnasal microsurgery in acromegaly. The current reports on surgical remissions, according to the strict criteria with international consensus using age- and sex-related normal levels for insulin-like growth factor-I and suppression of growth hormone (GH) with oral glucose tolerance below 1 mug/l, are more or less agreeable with values between 34 and 74%. In microadenomas (<10 mm in diameter), 59-95% remissions are published. Some improvement might be achieved in macroadenomas which presently have a chance of 26-68% to be satisfactorily operated on. Special instruments introduced by us to visualize and remove partially invasive adenoma parts are described. Intraoperative magnetic resonance imaging is discussed. With intraoperative measurement of GH, small adenoma rests <3 mm can be diagnosed. When GH did not sufficiently decline, an additional tumor search resulted in a significant improvement in results in resectable macroadenomas. With these techniques, we achieved remission rates which can hardly be further increased (micros 95%, macros 68%). In grossly invasive grade 4 adenomas, which are frequent in our unit, only an 80-95% reduction in tumor mass is feasible. Preoperative treatment with somatostatin analogues as used in most of our patients reduces the comorbidity and facilitates adenoma removal which is still controversially discussed in the literature. The complication rate of microsurgery in experienced hands is low.
 ...
PMID:Transsphenoidal microsurgery for newly diagnosed acromegaly: a personal view after more than 1,000 operations. 1704 88

The currently available long-acting somatostatin analogs normalize serum growth hormone (GH) levels and insulin-like growth factor-I levels in approximately 60% of patients with acromegaly. The recently introduced GH receptor antagonist, pegvisomant, is able to normalize insulin-like growth factor-I levels in virtually all acromegalic subjects. Although no correlation between increased GH concentrations and tumor size has been found, long-term safety studies are still in progress. Also, pegvisomant monotherapy is administered once daily and is very costly. Combined treatment of a somatostatin analog with pegvisomant appears to be an effective and rational approach.
 ...
PMID:Growth hormone receptor antagonists. 1704 92

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are implicated in the aberrant cell growth and pathological neovascularization that characterises proliferative diabetic retinopathy. While serum levels of IGF-I are reported to be either high or low in diabetic patients, there is evidence that local tissue levels of IGF-I may be more relevant to diabetic retinal pathology. IGF-I and IGF binding proteins (IGFBP) are expressed throughout the retina in vascular, neuronal and glial cells, and are altered in response to hyperglycaemia and hypoxia. Further support for a pathological role for local IGF-I comes from studies showing IGF-I to be increased in the vitreal fluids of patients with proliferative diabetic retinopathy. IGF-I may exert its cell growth promoting properties by stimulating a number of pathways including protein-kinase B (Akt), nuclear factor kB (NF-kappaB)/AP-1 and hypoxic-inducible factor-1alpha (HIF-1alpha). In addition, other growth factors may participate in IGF-I induced cell growth including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF). The importance of the GH/IGF system in diabetic retinopathy and retinal neovascularization has been highlighted by the use of agents that inhibit the system. GH receptor antagonists, GH receptor antisense oligonucleotides, somatostatin analogues and receptor neutralising antibodies to IGF-I reduce hypoxic-induced retinal neovascularization. These approaches may also prove to have benefits for improving vascular patency and vision in patients with diabetic retinopathy.
 ...
PMID:The role of growth hormone, insulin-like growth factor and somatostatin in diabetic retinopathy. 1716 53

Growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis is not only involved in the regulation of somatic growth but also has important physiological functions in adults. Several studies have shown that GH deficiency in adults is associated with abnormalities in body composition, metabolic derangements, and suboptimal physical performance. Furthermore, GH/IGF-I axis plays an important role in the maintenance of heart structure and function. Until recently, GH therapy was only used to treat short stature children, with or without established GH deficiency, and it remains common practice to discontinue GH replacement therapy when final height is achieved. Acromegaly, entity characterized by GH hypersecretion, is associated with an increased risk of premature death. Cardiac complications are known to be major determinants of the shortened life expectancy. Treatment of acromegaly accounts for a substantial decrease in morbidity and mortality. Surgery, radiation therapy and bromocriptine have only been able to reduce GH levels to normal levels in 10-30% of patients. The synthesis of somatostatin analogs has provided a new approach to acromegaly treatment. These drugs reduce GH and IGF-I levels in 80% of cases and normalize them in 40-60% of cases. Finally, GH/IGF-I system improves left ventricular systolic function and has also indirect effects on the cardiovascular system, mainly as a consequence of the peripheral vasodilatation. These effects are important in the understanding of the potential role of GH on improving ventricular systolic dysfunction and point to the use of GH as a potential therapy for chronic heart failure. The aim of the present review is to provide an update overview describing the role of GH on acromegaly, adult GH deficiency and heart failure, as well as the influence of GH-based therapy on heart structure and function.
 ...
PMID:Pharmacologic therapy in growth hormone disorders and the heart. 1758 52

Growth hormone (GH) secretion and serum insulin-like growth factor-I (IGF-I) decline with aging. This study addresses the role played by the hypothalamic regulators in the aging GH decline and investigates the mechanisms through which growth hormone secretagogues (GHS) activate GH secretion in the aging rats. Two groups of male Wistar rats were studied: young-adult (3 mo) and old (24 mo). Hypothalamic growth hormone-releasing hormone (GHRH) mRNA and immunoreactive (IR) GHRH dramatically decreased (P < 0.01 and P < 0.001) in the old rats, as did median eminence IR-GHRH. Decreases of hypothalamic IR-somatostatin (SS; P < 0.001) and SS mRNA (P < 0.01), and median eminence IR-SS were found in old rats as were GHS receptor and IGF-I mRNA (P < 0.01 and P < 0.05). Hypothalamic IGF-I receptor mRNA and protein were unmodified. Both young and old pituitary cells, cultured alone or cocultured with fetal hypothalamic cells, responded to ghrelin. Only in the presence of fetal hypothalamic cells did ghrelin elevate the age-related decrease of GH secretion to within normal adult range. In old rats, growth hormone-releasing peptide-6 returned the levels of GH and IGF-I secretion and liver IGF-I mRNA, and partially restored the lower pituitary IR-GH and GH mRNA levels to those of young untreated rats. These results suggest that the aging GH decline may result from decreased GHRH function rather than from increased SS action. The reduction of hypothalamic GHS-R gene expression might impair the action of ghrelin on GH release. The role of IGF-I is not altered. The aging GH/IGF-I axis decline could be rejuvenated by GHS treatment.
 ...
PMID:Insights into a role of GH secretagogues in reversing the age-related decline in the GH/IGF-I axis. 1768 5

This article examines the role of pegvisomant in the treatment of acromegaly. This syndrome, caused by excessive growth hormone (GH) secretion by a pituitary adenoma, is associated with a doubled mortality rate and poor quality of life. Pituitary microsurgery has long been the first choice of treatment since it cures many patients, especially those with localized tumors. Adjuvant irradiation was given if insulin-like growth factor-I (IGF-I) or GH did not normalize. The introduction of long-acting slow- release somatostatin analogs was a breakthrough for adjuvant treatment, although not always effective. Rather, targeting excessive GH production, muting the GH signal at its receptor, was a totally different approach. The development of GH antagonists (by mutation ofglycine at position 120) and other modifications to enhance receptor binding, and subsequent pegylation of the molecule led to the development of B2036. After pegylation of B2036 at 5 positions the distribution volume is restricted and its serum half-life considerably increased. In short-term clinical studies performed in selected, mostly pretreated, acromegalic patients, IGF-I normalized in the majority of cases. Combination therapy with long-acting somatostatin analogs and weekly rather than daily pegvisomant injections appears to be successful in one clinical study and might limit the high cost of pegvisomant. Long-term efficacy and safety has to be demonstrated. The drug does not cross the blood-brain barrier, and whether it distributes freely into the extracellular space of other organs than the liver has not been investigated, which might have implications for persistent local IGF-I production under unrestrained GH concentrations.
 ...
PMID:Nanomedicines in the treatment of acromegaly: focus on pegvisomant. 1772 73

Rainbow trout gill tissue was used to examine the role of somatostatin (SS) on insulin-like growth factor-I (IGF-I) receptor expression. In vivo implantation of fish with somatostatin-14 (SS-14) reduced expression of IGF-I receptor mRNAs as well as [(125)I]-IGF-I binding. In vitro incubation of gill filaments with SS-14 or various SS isoforms, including SS-28 and [Tyr(7), Gly(10)]-SS-14-containing peptides, directly inhibited IGF-I receptor mRNA expression. SS-14 also inhibited [(125)I]-IGF-I binding in vitro. These data indicate that SSs inhibit the mRNA and functional expression of IGF-I receptors in gill, and suggest that SSs regulate growth in an extrapituitary manner by reducing sensitivity to IGF-I.
 ...
PMID:Somatostatin inhibits insulin-like growth factor-I receptor expression in the gill of a teleost fish (Oncorhynchus mykiss). 1788 Sep 45

Growth of vertebrates is controlled by the growth hormone (GH)-insulin-like growth factor-I (IGF-I) system, and somatostatins (SSs) have been shown to inhibit growth by reducing the release of growth hormone (GH) from the pituitary. In this study, we used rainbow trout to assess the effects of SSs on the production of IGF-I. Somatostatin-14 (SS-14-I) implantation for 15 days significantly reduced steady-state levels of IGF-I mRNA in liver and lowered IGF-I concentration in plasma compared to control animals. The direct effects of SSs were examined on hepatocytes incubated in vitro. SS-14-I inhibited basal and GH-stimulated IGF-I mRNA expression. SS-14-I inhibition of GH-stimulated IGF-I expression was concentration- and time-dependent; the ED(50) was ca. 40 ng/ml and the maximum response was observed after 6h. All SS isofoms tested, including the N-terminally extended form of SS-14-I, SS-28-I, and the [Tyr(7), Gly(10)]-substituted forms of SS, SS-14-II, SS-25-II and SS-28-II, inhibited GH-stimulated IGF-I mRNA expression. The inhibitory effects of SS-14-I on steady-state levels of IGF-I mRNA resulted from reduced IGF-I mRNA transcription and not from altered mRNA stability. SS-14-I also reduced basal and GH-stimulated release of IGF-I into culture medium. These results indicate that SSs regulate growth in an extrapituitary manner by reducing hepatic IGF-I biosynthesis and secretion.
 ...
PMID:Somatostatin inhibits basal and growth hormone-stimulated hepatic insulin-like growth factor-I production. 1800 45

Alzheimer's disease (AD) is characterized by the cerebral deposition of senile plaques that are mainly composed of a set of peptides referred to as amyloid beta-peptides (Abeta). Among the numerous neuropeptides produced in intrinsic cortical and hippocampal neurons, somatostatin (SRIF) has been found to be the most consistently reduced in the brain and cerebrospinal fluid of AD patients. SRIF receptors (SSTR), which mediate the neuromodulatory signals of SRIF, are also markedly depleted in the AD brain, there being subtype-selective alterations in cortical areas. In the rat temporal cortex, we have shown that intracerebroventricular infusion of Abeta25-35 results in a decrease in SRIF-like immunoreactivity and in SRIF receptor subtype 2 (SSTR2) mRNA and protein levels, in correlation with a decrease in SSTR functionality. Insulin-like growth factor-I prevents the reduction in these parameters induced by Abeta25-35. Abeta has recently been demonstrated to be degraded primarily by a neutral endopeptidase, neprilysin, in the brain. SRIF regulates brain Abeta levels via modulation of neprilysin activity. Because SRIF expression in the brain declines upon aging in various mammals, including rodents, apes and humans, the aging-dependent reduction of SRIF has been hypothesized to trigger accumulation of Abeta in the brain by suppressing neprilysin action. Here we present an overview of recent advances on the role of SRIF in AD and its relationship with Abeta peptides.
 ...
PMID:Somatostatin and Alzheimer's disease. 1835 53

Lanreotide Autogel (ATG) [Somatuline Depot] is a novel, long-acting preparation of the somatostatin analogue lanreotide acetate that acts via somatostatin receptors to reduce both growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels. It is indicated for the management of acromegaly and, relative to most other licensed agents, it has a favourable pharmacokinetic profile that permits administration once every 28-42 days. Subcutaneous lanreotide ATG was an effective and generally well tolerated treatment in patients with acromegaly in well designed trials and extension studies of up to 4 years duration. It was shown to be no less effective than intramuscular lanreotide long-acting (LA) microparticles treatment in these studies, with more limited data showing that lanreotide ATG therapy was as effective as intramuscular octreotide long-acting repeating (octreotide LAR) treatment. While both of these latter agents offer the advantage of treatment once every 28 days, lanreotide ATG also has the advantage of being available in a convenient pre-filled syringe and is given subcutaneously rather than intramuscularly like other somatostatin analogues. Thus, it provides a valuable first-line option for the management of patients with acromegaly.
 ...
PMID:Lanreotide Autogel: a review of its use in the management of acromegaly. 1837 Apr 50


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