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)

Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in IGF-I, and mortality is lowered following normalization of IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of acromegaly have not considered recent advances in medical therapy, in particular, the place of pegvisomant, a GH receptor antagonist. Treatment goals include normalizing biochemical markers, controlling tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces tumor volume and is considered first-line therapy. Radiation reduces tumor volume and GH and IGF-I levels, but the onset of action is slow and hypopituitarism typically develops. Therefore, pharmacotherapy is often used following surgery or as first-line therapy for nonresectable tumors. Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-prolactin-cosecreting tumors but will not achieve hormone normalization in most patients. Somatostatin analogs effectively suppress GH and IGF-I in most patients, but intolerance (e.g. diarrhea, cramping, gallstones) can occur. Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes IGF-I levels, reduces signs and symptoms, and corrects metabolic defects. Pegvisomant does not appear to affect tumor size and has few adverse effects. Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs.
 ...
PMID:Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm. 1455 52

Acromegaly is a rare disabling disorder that results in premature death. The excess mortality and morbidity are the result of prolonged elevation of growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, and vigorous control of these improves well-being and restores life expectancy to normal. Recognition of the benefits of treatment has emphasised the need for optimal control of the GH/IGF-I axis. Transsphenoidal surgery is first-line therapy in the majority of patients; however, as most tumours are macroadenomas, cure rates are low. The role of radiotherapy is evolving and, although extremely effective at controlling tumour growth, it can take up to 15 years to control GH & IGF-I levels. In the interim, medical therapy is necessary. Dopamine agonists are inexpensive oral agents but, although most patients experience some benefit, GH and IGF-I levels are only normalised in around 35-40% of patients, and side effects are common. Somatostatin analogues are the gold standard of medical treatment. They can induce tumour shrinkage in a proportion of patients and can normalise the GH/IGF-I axis (at best) in approximately 65% of individuals; however, this leaves a significant cohort uncontrolled. The advent of the GH receptor antagonist pegvisomant provides the potential for IGF-I to be normalised in virtually every patient, but this novel form of therapy, which does not act on the pituitary, also raises many questions.
 ...
PMID:Medical treatment in acromegaly. 1464 22

Growth hormone (GH) and the insulin-like growth factor-I (IGF-I) play significant roles in pubertal development, menarche, the menstrual cycle, fertility, and reproduction. Growth hormone deficiency or insufficiency causes a delay in the onset of puberty and in its normal course unless treated with synthetic GH. It seems that GH affects the ovary during puberty both indirectly through the gonadotropins and IGF-I, and directly through its effect on steroidogenesis. The GH axis is activated by small increases in circulating estrogens, which initiate large increases in GH during puberty. The reproductive function of the female is also affected by GH. GH acts on the ovary affecting gametogenesis and steroidogenesis. GH receptor mRNA and protein have been found in ovarian cells, and this suggests that the direct action of GH provides an important modulatory effect on gonadotropin-dependent and -independent functions. It also affects the maturation of the follicle and gamete, and thereby plays a facilitatory role in fertility. The majority of women with GH-deficiency, but not all, require assisted reproductive technologies to induce ovulation. Many women with polycystic ovary syndrome (PCOS) have an impaired GH response to stimulation with Levo-Dopa and GH releasing hormone (GHRH). Hyperandrogenism in PCOS may contribute to the reduced GH secretion because testosterone directly stimulates somatostatin release. Reduction of the excessive androgens facilitates the dopaminergic control of GH. In conclusion, GH-insufficient states disrupt ovarian function, causing problems in sexual maturation, the menstrual cycle, and the reproductive ability of the female.
 ...
PMID:Growth hormone insufficiency and its impact on ovarian function. 1464 12

The neuroendocrine system integrates genotype with external factors such as nutrition to regulate animal growth. To investigate the role of somatotropic axis in the interaction of genotype and nutrition, two series of experiments were conducted using broiler and layer chickens as a model. In the first experiment, both strains of chickens were raised on their respective standard diets and the mRNA expressions of somatotropic genes were investigated on day 5 (D5), D21, and D42 after hatching as composites of genotype and nutrition. The hypothalamic somatostatin (SS) and pituitary growth hormone (GH) mRNA expression as well as the plasma GH levels were higher in layer chickens while the opposite was true for hepatic GH receptor (GHR) mRNA. Regulation of GHR mRNA expression was found to be tissue-specific. Hepatic GHR mRNA content increased with age whereas in the muscle, the peak levels of expression were observed at D5 with significantly higher abundance ratio in the layer. To evaluate genotype-diet interaction on growth and the patterns of gene expression of both layer and broiler chickens, layers were fed broiler diet and vice versa from D1 to 42 in the second experiment. The D42 body weight of layer chickens increased by 35% when fed with broiler diet, whereas that of broiler chickens decreased by 51% when fed with layer food. The diet exchange completely reversed the patterns of hypothalamic SS and pituitary GH mRNA expression and the strain differences vanished when the comparison was made on the same diet basis. The hepatic GHR mRNA decreased by 46.1% in broilers fed with layer food, but increased by 45.6% in the layer fed with broiler diet. The strain differences were diminished but did not completely disappear on the same diet basis for hepatic GH receptor mRNA. In contrast, however, the muscle GHR mRNA expression was not affected by diet exchange and thus, was more genotype-specific. The results suggest that genes of the somatotropic axis respond to nutrition differently at the level of transcription.
 ...
PMID:Effect of genotype-nutrition interaction on growth and somatotropic gene expression in the chicken. 1498 Jul 90

Pfizer (formerly Pharmacia), in collaboration with its wholly owned subsidiary Sensus, has developed and launched pegvisomant, a pegylated, genetically modified human growth hormone (hGH), for the treatment of acromegaly. Pegvisomant, in contrast to classical somatostatin analogs which lower hGH synthesis, exerts its anti-hGH action by preventing GH receptor activation. This drug is now available in the US and Europe for the treatment of acromegaly.
 ...
PMID:Pegvisomant Pfizer/Sensus. 1513 90

The treatment of patients with persistently active acromegaly has been facilitated over the past decade by the advent of highly specific and selective pharmacological agents. Somatostatin analogs, derived from the native inhibitory hormone somatostatin, are available in extended-duration preparations and are effective in reducing serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) as well as in improving the adverse clinical effects of acromegaly. Cabergoline, an agonist with a specificity for the dopamine D-2 receptor, has been shown to suppress IGF-I levels and induce tumor shrinkage in 35 and 50% of patients, respectively. The GH receptor antagonists compete with naturally occurring GH for binding with the GH receptor. As such, pegvisomant normalizes circulating IGF-I levels in 80 to 90% of patients with acromegaly. This last line of therapy should be considered for use in patients in whom surgery and medical therapy with somatostatin and/or dopamine agonists are either ineffective or poorly tolerated.
 ...
PMID:Pharmacological approach to the treatment of acromegaly. 1519 32

The treatment of acromegaly has changed considerably over the last few decades. In the late 1970s, the introduction of the dopamine receptor agonists made it possible to reduce growth hormone (GH) secretion by somatotropinomas for the first time. Thereafter, the introduction of the somatostatin analogues in the early 1980s had major implications. Recently, the first data on the use of genetically engineered human GH receptor (GHR) antagonists that block GH actions have become available. These GHR antagonists reduce both the biochemical abnormalities of acromegaly, as well as improve clinical signs and symptomatology. In this article we firstly review available data on dopamine agonists. Currently these compounds should be considered in patients with a mixed GH-prolactin secreting pituitary adenoma and/or those in whom pre-treatment insulin-like growth factor (IGF)-I concentrations are below 750 microg/L. We then discuss the somatostatin analogues. These compounds are capable of achieving biochemical control of GH and IGF-I in 50-60% of patients and tumour shrinkage in some 30%. In particular, candidates for treatment with these compounds are those patients who have undergone an unsuccessful transsphenoidal operation or who await the therapeutic effect of external pituitary irradiation. In selected patients primary medical therapy with somatostatin analogues is certainly a feasible option. To date, pegvisomant is the only available member of a new class of drugs that was especially designed to block the GHR. Pegvisomant is the most effective treatment for normalising IGF-I concentrations and appears to have a good safety profile. However, liver function tests should be regularly monitored and tumour size should be closely followed. Finally, we propose a treatment algorithm for acromegaly.
 ...
PMID:Pharmacological therapy for acromegaly: a critical review. 1530 64

Pegvisomant, a GH receptor antagonist, is a new pharmaceutical approach to acromegaly. It enables IGF-I levels to return in the age- and sex-reference range in approximately 90% of patients. This new approach is particularly beneficial in those patients who do not experience control of hormone hypersecretion after surgery and/or medical treatment with somatostatin analogs. In our preliminary experience, out of 16 patients unsuccessfully operated on by transsphenoidal surgery and resistant to 40-mg octreotide-LAR or 120-mg lanreotide for at least 6 months, 13 normalized their IGF-I levels within 6 months from treatment beginning. Normalization of IGF-I levels was accompanied by a significant decrease of ring size. We did not observe any increase of tumor remnant in this short period of treatment. In two cases we observed a significant increase of liver transaminases levels. In conclusion, more than 80% of patients with acromegaly unsuccessfully treated by surgery or currently available somatostatin analogs can achieve normal IGF-I levels after short-term treatment with pegvisomant.
 ...
PMID:The use of a GH receptor antagonist in patients with acromegaly resistant to somatostatin analogs. 1549 60

Mortality is increased in individuals with acromegaly unless serum growth hormone (GH) levels are below 2 microg/l and serum insulin-like growth factor (IGF)-I levels are normal following treatment. These combined criteria have been used to define remission of the disorder in this review. Transsphenoidal surgery achieves remission targets in an average of 55% of patients. For those not in remission following surgery, options include repeat surgery or use of adjuvant therapy. Fractionated external beam pituitary radiotherapy achieves 10-year remission rates of 47% but leaves patients exposed to excess GH until remission occurs. Stereotactic radiotherapy and gamma knife radiosurgery achieve remission rates of 40% over 3 years, and dopamine agonists produce remission in about 20% of patients. Somatostatin analogues induce remission in 59% of patients within the first year of treatment. The GH receptor antagonist pegvisomant leads to remission in 90% of patients, using IGF-I levels for assessment. Optimal treatment for a patient with acromegaly thus depends on the likely efficacy of treatment, cost, surgical skill, severity of side effects, tolerability, control of tumour growth, and improvement in complications related to tumour mass. A primary surgical approach, followed by medical therapy for those not in remission, remains the preferred option in most centres.
 ...
PMID:Treatment of acromegaly. 1553 5

Medical therapy plays an important role in the management of patients with acromegaly and is commonly used adjunctively after surgical resection of the pituitary tumor. Generally, surgery alone provides a 50 to 70% rate of cure; however, the outcome depends on the experience and ability of the surgeon and the characteristics of the tumor. The role of postsurgical medical therapy is to achieve long-term biochemical control of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. In some patients, medical therapies may be implemented sooner as primary or preoperative therapy. Somatostatin analogs have been the mainstay of medical therapy for acromegaly. The somatostatin analog octreotide produces normalization of IGF-I in approximately 50% of patients but is associated with gastrointestinal adverse effects, including the development of gallstones. Octreotide requires thrice-daily subcutaneous administration. Long-acting formulations of somatostatin analogs (octreotide LAR, lanreotide) are at least as effective and as well tolerated as short-acting octreotide. Unfortunately, some patients are suboptimally responsive to or become intolerant of these agents. Pegvisomant belongs to a new class of agents known as GH-receptor antagonists. This novel agent competitively binds to the GH receptor, blocking IGF-I production. Pegvisomant is highly effective in achieving normal IGF-I concentrations and in reducing signs and symptoms of acromegaly, even in patients resistant to previous treatments. Pegvisomant has been proved safe and well tolerated and has no effect on gallbladder motility. GH levels remain elevated. Transient elevations in liver enzyme levels require monitoring but rarely necessitate termination of therapy. Normalizing IGF-I concentrations with pegvisomant also may have a beneficial effect on carbohydrate metabolism and cardiovascular risk.
 ...
PMID:Role of medical therapy in the management of acromegaly. 1585 34


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