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)

Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The prevalence is estimated at 1:140,000-250,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected). Due to insidious onset and slow progression, acromegaly is often diagnosed four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet), widened thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth-hormone-releasing hormone (GHRH) responsible for pituitary hyperplasia. The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT) and by detection of increased levels of insulin-like growth factor-I (IGF-I). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly. Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain.
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PMID:Acromegaly. 1857 66

Lanreotide Autogel (ATG) [Somatuline Depot]The use of trade names is for product identification purposes only and does not imply endorsement. is a novel, long-acting preparation of the somatostatin analog 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 favorable 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) microparticle 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 analogs. Thus it provides a valuable first-line option for the management of patients with acromegaly.
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PMID:Spotlight on lanreotide Autogel in acromegaly. 1861 Oct 70

In this prospective study 16 cats with diabetes mellitus were examined for concurrent acromegaly by measuring plasma growth hormone (GH) and insulin-like growth factor-I concentrations, and magnetic resonance imaging (MRI) of the pituitary fossa. Additionally, the effects of octreotide administration on the plasma concentrations of glucose, GH, alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotrophic hormone (ACTH), and cortisol were measured. Five cats were diagnosed with hypersomatotropism. The pituitary was enlarged in these 5 cats and in 2 other cats. Six cats that required a maximum lente insulin dosage >or=1.5 IU/kg body weight per injection had pituitary enlargement and 5 of these cats had acromegaly. Plasma concentrations of GH, ACTH, and cortisol decreased significantly after single intravenous administration of the somatostatin analogue octreotide in the acromegalic cats. The effect on GH concentrations was more pronounced in some of the acromegalic cats than in others. In the non-acromegalic cats only ACTH concentrations decreased significantly. In both groups plasma glucose concentrations increased slightly but significantly, whereas alpha-MSH concentrations were not significantly affected. In conclusion, the incidence of hypersomatotropism with concomitant pituitary enlargement appears to be high among diabetic cats with severe insulin resistance. Some of these cats responded to octreotide administration with a pronounced decrease in the plasma GH concentration, which suggests that octreotide administration could be used as a pre-entry test for treatment with somatostatin analogues.
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PMID:Growth hormone excess and the effect of octreotide in cats with diabetes mellitus. 1880 40

The growth of prostate cancer is controlled by several hormones and growth factors. In cases of metastasized prostate cancer, antigonadotropic therapy is currently considered state-of-the-art treatment. Surgical therapies such as adrenalectomy and hypophysectomy are no longer in use. Nevertheless, hypophysectomy has proven efficacy for palliative pain treatment as well as increasing duration of survival. The authors present the case of a 63-year-old man with metastatic prostate cancer who presented with high serum prostate-specific antigen levels (1216 microg/L) and cavernous sinus syndrome. His disease was progressing despite leuprorelin and docetaxel therapy, and he had severe bone pain despite high-dose pain therapy. He was also anemic. Contrast-enhanced MR imaging showed a pituitary lesion as well as metastatic infiltration of the skull base including the cavernous sinus. The patient's serum level of prolactin was mildly elevated, testosterone was below the detection limit, and insulin-like growth factor-I (IGF-I) was in the upper range for a patient of his age (233 microg/L). Because of the elevated prolactin and high-normal IGF-I levels he was offered a hypophysectomy in addition to pituitary tumor removal. Histological examination of the resected lesion confirmed a nonsecreting pituitary adenoma with infiltration of prostate cancer cells. Postoperatively the patient's prostate-specific antigen levels dropped to 876 microg/L, his bone pain resolved, and the cavernous sinus syndrome improved. Nevertheless, he died of septicemia 4 months after surgery. Older publications as well as this case have shown the benefit of hypophysectomy for pain treatment. A reduction of IGF-I levels even in the final stage metastasized prostate cancer may play a major role. Respectively, clinical studies with somatostatin analogs are currently in progress, which may lead to a "new" way of treatment in these otherwise hopeless patients. On the basis of the pain relief seen after hypophysectomy in this case and similar benefits reported in older publications, the authors raise the question whether this treatment should be offered more frequently, and whether additional medical options of hormone treatment may be beneficial in similar cases.
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PMID:Hypophysectomy for prostate cancer: a revival of old knowledge? 1882 67

Acromegaly is a rare disease usually caused by growth hormone (GH) hypersecretion, due to a pituitary adenoma; in very rare cases, acromegaly is due to ectopic secretion of GHRH, responsible for pituitary hyperplasia. Owing to its insidious onset, acromegaly is often diagnosed late (4 to > 10 years after onset), at an average age of about 40 years, in front of an acquired, slowly progressing disfigurement mainly involving the face and extremities. Acromegaly has also rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. The diagnosis is based on an increased serum GH concentration unsuppressed following an oral glucose load (oral glucose tolerance test -OGTT-) and an increased insulin-like growth factor-I (IGF-I); according to a 2000 Consensus statement, if the basal serum GH is above 0,4microg/L (1.2mIU/L) and/or if the IGF-I is elevated, an OGTT must be performed. If the lowest GH value (nadir) during OGTT remains above 1microg/L (3mIU/L), acromegaly is confirmed. With the generalized use of very sensitive assays nowadays, it has recently been considered that this cutoff should be decreased to 0,3microg/L (0.9mIU/L). Treatment is aimed at correcting (or preventing) tumor compression by excising the culprit lesion, and at reducing GH and IGF-I levels to normal values (or at least to a "safe" GH level of < 2microg/L or < 6mIU/L). A stepwise therapeutic strategy is used: transsphenoidal surgery is often the first-line treatment; when surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used, somatostatin analogs being generally preferred; the GH antagonist (pegvisomant) is used in patients that are resistant or intolerant to somatostatin analogs. Prognosis of acromegaly has improved in the recent years: adequate hormonal disease control is achieved in most cases, allowing life expectancy similar to that of the general population.
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PMID:[Acromegaly]. 1900 12

Physiologists have routinely used understanding of the immune system to generate antibodies against regulatory molecules, growth factors, plasma membrane receptors, and other mammalian molecules in the development of analytical tools and assays. In taking this notion further, antibodies have been used in vivo to modulate physiological systems and to improve our understanding of their molecular interactions. To develop antibodies with physiological activity (efficacy), physiologists have worked with immunologists in developing interdisciplinary insights, requiring basic knowledge of immune system function in designing strategies to generate antibodies that interact with endogenous molecules of physiological interest, in vivo. Antibodies in different physiological systems have been shown to enhance or inhibit endogenous molecular functions. Two approaches have been used: passive and active immunization. Antibodies in these contexts have provided tools to develop further insights into molecular physiological mechanisms. Perhaps surprisingly, enhancing antibodies have been developed against a diverse set of target molecules including several members of the growth hormone/insulin-like growth factor-I axes and those of the beta(2)-adrenoceptor axis. Antibodies that inhibit the actions of somatostatin have also been developed. A further novel approach has been the development of antibodies that interact with adipose cells in vivo. These have the potential to be used in therapeutic antiobesity approaches. Antibodies with efficacy in vivo have provided new insights into molecular physiological mechanisms, enhancing our understanding of these complex processes.
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PMID:Antibodies as molecular mimics of biomolecules: roles in understanding physiological functions and mechanisms. 1904 2

Here, we report the cloning and characterization of growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-II from naked carp (Gymnocypris przewalskii), a native teleost fish of Lake Qinghai in the Qinghai-Tibet Plateau of China. The GH of naked carp encodes for a predicted amino acid sequence showing identities of 63%, 63%, 91% and 94% with cherry salmon, rainbow trout, zebrafish and grass carp, respectively. Compared to common carp and goldfish, evolutionary analysis showed that genome duplication has had less influence on the relaxation of purifying selection in the evolution of naked carp GH. Sequence analysis of naked carp IGF-I (ncIGF-I) and ncIGF-II showed a high degree of homology with known fish IGF-I and IGF-II. To investigate effects of salinity and ionic composition of the aquatic environment on the GH-IGF axis in naked carp, male fish held in river water were assigned randomly to 4 groups: RW (river-water), RW+Na (NaCl in RW), RW+Mg (MgCl(2) in RW) and LW (lake-water) groups. The concentrations of Na(+) in RW+Na and Mg(2+) in RW+Mg were equal to the concentrations of these ions in lake-water. After 2 days of exposure, the plasma IGF-I levels in the RW+Na and LW groups were significantly higher than the control group (RW), and the plasma GH levels of the LW group were also significantly higher than the RW group. The somatostatin (SS) levels in the hypothalamus significantly increased in the RW+Na group. After 5 days of exposure, these hormone levels did not differ significantly among groups. These results indicate that while the plasma GH and IGF-I levels are osmosensitive, the absence of a change in GH secretion in RW+Na might be partly due to a transiently increased release of hypothalamic SS induced by the stress of neutral-saline water. This is the first report of a salinity-induced increase of GH-IGF-I circulating levels in Cypriniformes.
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PMID:Growth hormone and insulin-like growth factor of naked carp (Gymnocypris przewalskii) in Lake Qinghai: expression in different water environments. 1923 87

Birds have rapid pre- and post-hatching growth rates. The major hormones required to support normal growth are growth hormone (GH), triiodothyronine (T(3)) and insulin-like growth factor-I (IGF-I). Optimal growth requires a "set-point" concentration of both IGF-I and T(3) in the circulation. Pituitary GH plays a role in controlling the circulating concentrations of both IGF-I and T(3). Nutritional restriction (energy, protein) leads to reductions in circulating concentrations of both IGF-I and T(3) with increased GH secretion due removal of negative feedback. Similarly, there is un-coupling of the GH-IGF-I axis in stunting disease. A critical control point is at the level of the liver and GH receptor/signal transduction. The major hormones controlling metabolism include glucagon, insulin, adrenal glucocorticoid hormone, corticosterone and potentially somatostatin. Chickens and turkeys have higher circulating concentrations of glucose than those of livestock mammals. What are not known include the following: the biological basis for the high basal glucose concentrations; the quantitative fluxes of key metabolites in the fed and fasted state through growth and development; the relative contribution of different organs to gluconeogenesis; the relative importance of insulin and somatostatin in controlling lipolysis and the role of gastro-intestinal hormones in the control of metabolism.
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PMID:Perspectives on the endocrinology of poultry growth and metabolism. 1939 57

Control of postnatal growth is the main, but not the only, role for growth hormone (GH) as this hormone also contributes to regulating metabolism, reproduction, immunity, development, and osmoregulation in different species. Likely owing to this variety of group-specific functions, GH production is differentially regulated across vertebrates, with an apparent evolutionary trend to simplification, especially in the number of stimulatory factors governing substantially GH release. Thus, teleosts exhibit a multifactorial regulation of GH secretion, with a number of factors, from the newly discovered fish GH-releasing hormone (GHRH) to pituitary adenylate cyclase-activating peptide (PACAP) but also gonadotropin-releasing hormone, dopamine, corticotropin-releasing hormone, and somatostatin(s) directly controlling somatotropes. In amphibians and reptiles, GH secretion is primarily stimulated by the major hypothalamic peptides GHRH and PACAP and inhibited by somatostatin(s), while other factors (ghrelin, thyrotropin-releasing hormone) also influence GH release. Finally, in birds and mammals, primary control of GH secretion is exerted by a dual interplay between GHRH and somatostatin. In addition, somatotrope function is modulated by additional hypothalamic and peripheral factors (e.g., ghrelin, leptin, insulin-like growth factor-I), which together enable a balanced integration of feedback signals related to processes in which GH plays a relevant regulatory role, such as metabolic and energy status, reproductive, and immune function. Interestingly, in contrast to the high number of stimulatory factors impinging upon somatotropes, somatostatin(s) stand(s) as the main primary inhibitory regulator(s) for this cell type.
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PMID:Understanding the multifactorial control of growth hormone release by somatotropes: lessons from comparative endocrinology. 1945 35

Excessive production of the growth hormone (GH) is responsible for acromegaly. It is related to a pituitary GH-secreting adenoma in most cases. Prevalence is estimated 40-130 per million inhabitants. It is characterised by slowly progressive acquired somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The rheumatologic, cardiovascular, respiratory and metabolic consequences determine its prognosis. The diagnosis is confirmed by an increased serum GH concentration, unsuppressible by an oral glucose load and by detection of increased levels of insulin-like growth factor-I (IGF-I). Treatment is aimed at correcting (or preventing) tumour compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. When surgery, the usual first-line treatment, fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogues and/or radiotherapy can be used. The GH-receptor antagonist (pegvisomant) is helpful in patients who are resistant to somatostatin analogues. Thanks to this multistep therapeutic strategy, adequate hormonal disease control is achieved in most cases, allowing a normal life expectancy.
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PMID:Pituitary tumours: acromegaly. 1994 23


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