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 a disorder caused by excessive secretion of human growth hormone (GH). Somatostatin and its analogue-prolonged release formulation, lanreotide (Somatuline PR), inhibit the secretion of growth hormone. The aim of this open Phase III study was to investigate the clinical efficacy of lanreotide in the treatment of six acromegalic patients with a mean age of 44 +/- 13 yr including two patients with diabetes mellitus. All the patients previously received transsphenoidal or transcranial hypophysectomy. Lanreotide was given intramuscularly every 2 weeks at a fixed dose of 30 mg for 12 weeks. Serum GH and insulin-like growth factor-I (IGF-I) levels were evaluated before, 2, 6 and 12 weeks after treatment. After 12 weeks of treatment, mean (+/- SEM) GH levels decreased from 24.8 +/- 12.5 to 6.9 +/- 3.3 ng/ml and mean serum IGF-I levels decreased from 689 +/- 282 to 430 +/- 216 ng/ml. Abdominal ultrasonographic examinations showed no gallbladder stone or bile sand formation before or after the treatment. Three of the patients who did not receive octreotide presented with manifestations of mild gastrointestinal adverse effect such as mild abdominal pain and diarrhea. In conclusion, lanreotide is effective in the treatment of active postoperative acromegaly.
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PMID:An open, phase III study of lanreotide (Somatuline PR) in the treatment of acromegaly. 1042 87

The neuroregulation of growth hormone (GH) secretion and the state of the adipose tissue reserves are closely related. GH exerts lipolytic actions on the adipose tissue and low body weight enhances secretion of GH while obesity is associated with reduced levels of GH and blocked release of GH when challenged by all stimuli. The mediators of the regulation exerted by the adipose tissue on the GH/insulin-like growth factor-I axis are not fully understood, but in the last few years two relevant factors have emerged--free fatty acids (FFA) and the adipocyte-produced hormone leptin. FFA and GH integrate a classical feedback loop and a rise in FFA blocks GH secretion. This action is rapid, dose-related and exerted at the pituitary level with no evident hypothalamic participation. A pharmacological reduction in FFA enhances secretion of GH and eliminates the GH blockade of obesity and Cushing's syndrome. The discovery of leptin has expanded our knowledge of the way in which the adipose tissue participates in some neuroendocrine actions. Obesity is associated with elevated levels of serum leptin while undernutrition and fasting lead to low leptin. In fasted rats, the pattern of GH pulsatility is eliminated with a near absence of spontaneous peaks, but the administration of leptin by the intracerebroventricular (i.c.v.) route restores the altered pattern. When fed rats receive antileptin antibodies i.c.v the normal pattern is reversed to an absence of pulses, reminiscent of the fasting state. These results are the first demonstration that, at least in experimental animals, leptin is a relevant factor in GH regulation. Leptin has no direct pituitary action and its action at the hypothalamic level appears to be mediated by neuropeptide Y, being the final step in a reduction in the somatostatin tone. On the other hand, the action of GH on leptin levels seems to be tenuous in humans, but in the near future it will be possible to investigate the action of leptin on human GH. As the hypothalamic neuroregulation of GH secretion in humans is unlike that in the rat, a crucial point for elucidation will be the actions, if any, and the mechanisms by which leptin participates in GH regulation in humans, as well as its alterations in disease states.
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PMID:Regulation of growth hormone secretion by signals produced by the adipose tissue. 1044 66

Growth hormone (GH) modulates the hypothalamic release of somatostatin and GH-releasing hormone; however, there has been no evidence of GH autoregulation on the pituitary somatotroph. To determine the effects of GH on its own regulation, we examined the pituitaries of giant transgenic mice expressing a GH agonist (E117L), dwarf transgenic mice expressing a GH antagonist (G119K), and dwarf mice devoid of the GH receptor/binding protein (GHR/BP). In the E117L transgenic mice, the number and distribution of pituitary GH-immunoreactive cells were unchanged from nontransgenic littermate controls; an ultrastructural examination revealed typical, densely granulated somatotrophs. In contrast, the pituitaries of the G119K mice contained both moderately granulated somatotrophs and a sparsely granulated (SG) population with well-developed synthetic organelles and a distinct juxtanuclear globular GH-staining pattern. GHR/BP-deficient mice exhibited a marked reduction in the intensity of cytoplasmic GH immunoreactivity; however, prominent GH staining in the juxtanuclear Golgi was seen. GH-immunoreactive cells were increased in number, and the reticulin network pattern was distorted; stains for proliferating cell nuclear antigen confirmed mild hyperplasia. Electron microscopy showed that the somatotrophs were hyperactive SG cells with prominent endoplasmic reticulum membranes, large Golgi complexes, and numerous mitochondria. These findings are consistent with synthetic and secretory hyperactivity in pituitary somatotrophs due to the reduced GH feedback regulation. The changes are most striking in animals that are devoid of GHR/BP and less marked in animals expressing a GH antagonist; both models had reduced insulin-like growth factor-I levels, but the more dramatic change in the GHR/BP animals can be explained by abrogated GH signaling. This represents the first evidence of direct GH feedback inhibition on pituitary somatotrophs, which may have implications for the use of GH analogs in different clinical settings.
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PMID:Evidence for growth hormone (GH) autoregulation in pituitary somatotrophs in GH antagonist-transgenic mice and GH receptor-deficient mice. 1070 16

The present study was aimed to compare antiproliferative effects of somatostatin (SS) and gonadotropin-releasing hormone analogs (GnRHa) on a fibroblast cell line. Proliferation index, cell count, viability of the cells and insulin-like growth factor-I (IGF-I) immunoreactivity were determined after treatment with either SS (100 microM/ml), GnRHa (35 nM/ml) or SS and GnRHa of Balb-C 3T3 mouse fibroblasts. It was found that the proliferation index, cell count, viability and IGF-I immunoreactivity were not affected by GnRHa treatment as compared with no treatment (p > 0.05). Application of SS to the fibroblasts resulted in a significant reduction in proliferation index, cell count, and IGF-I immunoreactivity as compared with GnRHa treatment and no treatment, but it had no effect on cell viability. The labelling index in SS-treated cells was significantly reduced as compared with combined treatment with SS and GnRHa. In conclusion, a direct effect of GnRHa on fibroblast cells in culture could not be demonstrated. SS had direct inhibitory effects on cell proliferation possibly via inhibition of IGF-I effects without affecting cell viability.
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PMID:Antiproliferative effects and insulin-like growth factor-I expression in Balb-C 3T3 fibroblasts after treatment with somatostatin and gonadotropin-releasing hormone analogs. 1099 71

Somatotrope function requires consideration of both growth hormone (GH) secretion and cellular proliferation. The regulation of these processes is, to a large extent, controlled by three hypothalamic hormones: GH-releasing hormone (GHRH), somatostatin (SRIF), and an as-yet-unidentified GH secretagogue (GHS). Each binds to G protein-linked membrane receptors through which signaling occurs. Our laboratory has used a series of genetic and transgenic models with perturbations of individual components of the GH regulatory system to study both somatotrope signaling and proliferation. Impaired GHRH signaling is present in the lit mouse, which has a GHRH receptor (R) mutation, and the dw rat, which has a post-receptor signaling defect. Both models also have impaired responses to a GHS, implying an interaction between the two signaling systems. The spontaneous dwarf rat (SDR), in which a mutation of the GH gene results in total absence of the hormone, shows characteristic changes in the hypothalamic regulatory hormones due to an absence of GH feedback and alterations in the expression of each of their pituitary receptors. Treatment of SDRs with GHRH and a GHS has allowed demonstration of a stimulatory effect of GHRH on GHRH-R, GHS-R, and SRIF type 2 receptor (SSTR-2) expression and an inhibitory effect on SSTR-5 expression. GH also modifies the expression of these receptors, though its effects are seen at later time periods and appear to be indirect. Overall, the results indicate a complex regulation of GH secretion in which somatotrope receptor, as well as ligand expression, exerts an important physiological role. Both the SDR and the GH-R knockout (ko) mouse have small pituitaries and decreased somatotropes, despite elevated GHRH secretion and intact GHRH-R signaling. Introduction of the hGHRH transgene into GH-R ko mice confirmed that the proliferative effects of GHRH require GH/insulin-like growth factor-I (IGF-I) action. The results offer new insights into factors participating in somatotrope proliferation.
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PMID:Secretagogues and the somatotrope: signaling and proliferation. 1103 41

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

The activity of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis undergoes marked variations across the human life span, mainly reflecting age-related changes in the neural control of somatotroph function. IGF-I secretion generally reflects GH status, except in newborns, who secrete high levels of GH but low levels of IGF-I. Changes in the gonadal steroid milieu, particularly estradiol, play a major role in the enhanced activity of the GH-IGF-I axis at puberty and probably reflect further changes in the neuroendocrine control of somatotroph secretion. The change in responsiveness of somatotrophs to various stimuli, including GHRH, is not as marked as the spontaneous secretion of GH at puberty. However, in childhood, somatotrophs are unusually refractory to the somatostatin-mediated negative GH autofeedback mechanism. Normal children show normal responsiveness to the stimulatory influence of alpha-adrenergic and cholinergic agonists, galanin and arginine, but the activating effect of these stimuli on somatotroph secretion is reduced in elderly individuals, with the notable exception of arginine. Arginine potentiates both spontaneous and GHRH-induced GH secretion to the same extent in normally growing children, adults and elderly individuals, indicating that the releasable pool of GH is generally preserved across the human life span. Thus, the reduction in spontaneous and GHRH-induced GH secretion in the elderly probably reflects age-related changes in neurotransmitter control, leading to GHRH hypoactivity and absolute or relative somatostatin hyperactivity in the aged hypothalamus. Cholinergic impairment in the aging brain probably involves hypothalamic pathways and leads to decreased activity of the GH-IGF-I axis in normal and elderly individuals, as well as in individuals with premature brain aging. However, there is evidence indicating that age-related variations in the activity of the natural GH-secretagogue ligand(s) at the hypothalamic level could also play a role in the age-dependent changes in the GH-IGF-I axis.
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PMID:Hypothalamic growth hormone-insulin-like growth factor-I axis across the human life span. 1120 26

This paper describes a 6-year-old Simmental bull with diabetes mellitus. The animal was referred to our clinic because of severe weight loss and chronic indigestion. Clinical examination revealed markedly disturbed general condition, impaired forestomach function and polyuria. There was aciduria, glucosuria and ketonuria. The most important biochemical findings were severe hyperglycemia, markedly increased activities of hepatic enzymes and severe metabolic acidosis. Plasma concentrations of insulin, insulin-like growth factor-I, thyroxine and 3,5,3'-triiodothyronine were lower than normal, whereas those of glucagon were higher than normal. Based on these findings, a diagnosis (secondary) diabetes mellitus was made. The bull was slaughtered and histological examination revealed mixed cell pancreatitis with severe degeneration of islet cells. Immunohistochemical examination of the pancreas showed that very few insulin-, glucagon-, somatostatin- and pancreatic polypeptide, insulin-like growth factor-I and adrenomedullin-producing islet cells were present.
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PMID:[Diabetes mellitus caused by pancreatitis in a bull]. 1123 31

Growth hormone secretagogues (GHSs) represent attractive therapeutic alternatives to recombinant growth hormone (GH), given their ability to amplify pulsatile hormone secretion in a relatively physiologic manner. CP-424,391 (391) is a novel, orally active pyrazolinone-piperidine [corrected] GHS. In rat pituitary cell cultures, 391 stimulated GH release with an EC50 = 3 nM. The addition of 391 to rat pituitary cells activated intracellular calcium signaling but did not elevate intracellular cyclic adenosine monophosphate (cAMP). 391 also modulated the effects of GH-releasing hormone and somatostatin on pituitary cell GH-release and intracellular signaling. In nonpituitary cell lines, the ability of 391 to stimulate intracellular signaling was dependent on the expression of recombinant human GHS receptor. Acute administration of 391 to anesthetized rats or to conscious dogs induced pulsatile release of G H in a dose-dependent manner. Plasma insulin-like growth factor-I (IGF-I) was elevated progressively over a 5-d course of daily oral dosing in dogs. Chronic oral administration of 391 augmented body weight gain in rats and dogs. Thus, the peptidomimetic GHS 391 has potential utility for the treatment of clinical conditions that could benefit from systemic augmentation of GH and IGF-I levels.
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PMID:Preclinical pharmacology of CP-424,391, an orally active pyrazolinone-piperidine [correction of pyrazolidinone-piperidine] growth hormone secretagogue. 1132 94

Immobilization of an extremity causes skeletal muscle atrophy and a dramatic increase in bone resorption. Growth hormone (GH) is known to play an important role in bone remodeling mediated in part by local insulin-like growth factor-I (IGF-I). In this study, we investigated changes in the levels of GH and IGF-I peptide in bone extracts from the femur after hind-limb immobilization for 5 days, 2, 4, and 8 weeks. The levels of somatostatin, which interacts with GH, were also measured in the bone extracts. GH levels increased after 8 weeks of hind-limb immobilization whereas the IGF-I concentrations increased after 2 weeks, but returned to control levels at 4 weeks, and decreased after 8 weeks of immobilization. The somatostatin levels in the bone extracts increased only after 8 weeks of hind-limb immobilization. Our findings suggest that, after hind-limb immobilization, changes in the concentrations of GH, IGF-I, and somatostatin in bone may mediate bone resorption either directly or through interaction with other factors.
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PMID:Changes in tissue levels of growth hormone, insulin-like growth factor-I, and somatostatin in the femurs of hind-limb immobilized rats. 1137 51


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