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)

Pulsatile GH secretion is exquisitely sensitive to perturbations in nutritional status, but the underlying mechanisms are largely unknown. Leptin, a recently discovered adipose cell hormone, is thought to be a sensor of energy stores and to regulate body mass, appetite, and metabolism at the level of the brain. Receptors for leptin are abundantly expressed in hypothalamic nuclei known to be involved in GH regulation, suggesting that leptin may serve as an important hormonal signal to the GH neuroendocrine axis in normal animals. To test this hypothesis, we examined the effects of intracerebroventricular infusion of recombinant murine leptin, at a dose of 1.2 microg/day for 7 days, on both spontaneous and GH-releasing hormone (GHRH)-stimulated GH secretion in free-moving adult male rats. Concomitant with suppressive effects on food intake, body weight, and basal plasma insulin-like growth factor I, insulin, and glucose concentrations, central infusion of leptin resulted in a 2- to 3-fold augmentation of GH pulse amplitude, 5-fold higher GH nadir levels, and a 2- to 3-fold increase in the integrated area under the 6-h GH response curve compared with those in vehicle-infused controls (P < 0.001). The intracerebroventricular infusion of leptin also produced a 3- to 4-fold increase in GHRH-induced GH release at GH trough times (P < 0.01). These studies demonstrate a potent stimulatory action of leptin on both spontaneous pulsatile GH secretion and the GH response to GHRH. The results suggest that the GH-releasing activity of leptin is mediated, at least in part, by an inhibition of hypothalamic somatostatin release. Thus, leptin may be a critical hormonal signal of nutritional status in the neuroendocrine regulation of pulsatile GH secretion.
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PMID:Leptin is a potent stimulator of spontaneous pulsatile growth hormone (GH) secretion and the GH response to GH-releasing hormone. 972 42

Ectopic GHRH-secreting tumors, such as carcinoid, rarely cause acromegaly. As protracted exposure to high levels of GH is associated with considerable morbidity and mortality, these patients require early and effective medical therapy to control hormonal hypersecretion. We employed a prolonged release somatostatin analog, lanreotide, to treat a patient with disseminated GHRH-producing carcinoid. Before treatment, the patient had a biochemical profile characteristic of active acromegaly. Plasma GHRH levels were markedly elevated (200-fold), and urinary 5-hydroxyindolacetic acid (5-HIAA) levels were increased (4-fold). Magnetic resonance imaging revealed a large asymmetrical pituitary mass consistent with somatotroph hyperplasia. Somatostatin receptor scintigraphy revealed multiple bony and soft tissue lesions as well as striking pituitary uptake. Lanreotide (30 mg) was administered weekly by im injection for 12 weeks. Rapid and sustained symptomatic clinical improvement with diminished soft tissue swelling and hyperhidrosis was observed. GHRH levels decreased by 70%; glucose-suppressed GH and insulin-like growth factor I levels were reduced by 90% and 75%, respectively, to near normal values; urinary 5-HIAA levels normalized; and the pituitary mass remained unchanged. Unfortunately, the patient died due to complications of osteogenic sarcoma. In conclusion, prolonged release lanreotide induced clinical and biochemical remission in this patient with diffusely metastatic GHRH-producing carcinoid. This long-acting drug thus offers an effective, well tolerated, and convenient medical therapy for control of hormonal hypersecretion induced by excess GHRH.
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PMID:Long-acting lanreotide induces clinical and biochemical remission of acromegaly caused by disseminated growth hormone-releasing hormone-secreting carcinoid. 1032 16

In adult female monkeys, serum concentrations of insulin-like growth factor I (IGF-I) are decreased by estradiol replacement, whereas levels of IGF-binding protein-3 (IGFBP-3) are increased. Furthermore, chronic IGF-I supplementation elevates serum IGFBP-3 despite a suppression of GH. To better understand how estradiol and IGF-I affect the IGF-I axis, a series of three studies was conducted to examine how estradiol and GH interact to affect the IGF-I axis and how IGF-I regulates IGFBP-1 and -3 during GH inhibition or receptor antagonism in adult female rhesus monkeys. In Exp 1, adult ovariectomized females were studied during a 28-day baseline condition and a 28-day treatment condition in which females received a constant s.c. infusion of a somatostatin analogue (octreotide, Sandoz; SSa; 6 microg/kg x day) with a 14-day washout period separating the two conditions. Within each 28-day phase, females were studied for 14 days with no estradiol replacement and for 14 days with estradiol replacement (3 microg/kg x day, s.c.). Treatment with estradiol and SSa alone significantly lowered serum IGF-I compared with baseline. In contrast, estradiol and SSa given in combination resulted in a significant increase in serum IGF-I. Serum IGFBP-3 was significantly increased by estradiol and the combination of estradiol and SSa. The response of serum GH to the acute administration of the excitatory amino acid analogue, n-methyl-D,L-aspartic acid (5 microg/kg, i.v.) was not differentially affected by any of the treatments. In Exp 2, the effects of a GH receptor antagonist (Trovert, Sensus Corp.) was assessed in ovariectomized, young adult, treated females (GHa; 1.0 mg/kg, s.c., weekly) and compared with that in untreated cohorts (Con) during 3 weeks of no estradiol and 3 weeks of estradiol replacement (3 microg/kg x day, s.c.). Serum IGF-I and IGFBP-3 were significantly suppressed in GHa compared with Con females. In Con females, estradiol replacement significantly decreased serum IGF-I and increased serum IGFBP-3. In contrast, estradiol replacement significantly elevated both serum IGF-I and IGFBP-3 in GHa females. In Exp 3, the effects of acute IGF-I administration (110 microg/kg, s.c.) were assessed during baseline conditions and during treatment with either GHa (1.0 mg/kg, s.c., weekly) or SSa (16 microg/kg, s.c. infusion) in young adult females during no estradiol replacement and during estradiol replacement (3 microg/kg x day, s.c.). Acute IGF-I administration produced a similar net increase in serum IGF-I during baseline and GHa or SSa treatment. Although serum IGFBP-3 was significantly reduced by both GHa and SSa, acute treatment with IGF-I produced a significant elevation in IGFBP-3, peaking by 3 h after treatment before returning to baseline at 7 h. Estradiol replacement elevated serum IGFBP-1 under baseline conditions as well as during GHa and SSa treatments. However, changes in serum insulin in response to the feeding patterns during the acute treatment with IGF-I, predicted changes in serum IGFBP-1. As GH secretion was inhibited during SSa, acute IGF-I had little effect on serum GH. Although acute IGF-I significantly suppressed serum GH by 3 h after treatment during baseline, the hypersecretion of GH during GHa treatment was unaffected by acute IGF-I. In conclusion, the results of the present analysis indicate that the effects of estradiol in postadolescent females on serum IGF-I are dependent on GH status, whereas estradiol consistently elevates serum IGFBP-3. Furthermore, acute IGF-I increases serum IGFBP-3 in females even during GH inhibition or receptor antagonism. Although overall serum concentrations of IGFBP-1 are elevated by estradiol and may be differentially affected by IGF-I treatment, acute changes in IGFBP-1 are more a consequence of changes in serum insulin in response to food intake. Taken together, these data suggest that IGFBP-3 is regulated by factors in addition to GH and that IGF-I can affect its own bioavailabi
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PMID:Effects of estradiol and exogenous insulin-like growth factor I (IGF-I) on the IGF-I axis during growth hormone inhibition and antagonism. 981 85

Experimental data suggest that elevated FFA levels play a leading role in the impaired GH secretion in obesity and may therefore contribute to the maintenance of overweight. GH has a direct lipolytic effect on adipose tissue; in turn, FFA elevation markedly reduces GH secretion. This suggests the existence of a classical endocrine feedback loop between FFA and GH secretion. However, the FFA mechanism of action is not yet understood. The involvement of somatostatin (SRIH) is controversial, and in vitro experiments suggest a direct effect of FFA on the pituitary. In sheep it is possible to collect hypophysial portal blood and quantify SRIH secretion in hypophysial portal blood under physiological conscious and unstressed conditions. In this study we determined the effects of FFA (Intralipid and heparin) infusion on peripheral GH and portal SRIH levels in intact rams chronically implanted with perihypophysial cannula and in rams actively immunized against SRIH to further determine SRIH-mediated FFA effects on GH axis. Immediately after initiation of Intralipid infusion, we observed a marked increase in the FFA concentration (2160 +/- 200 vs. 295 +/- 28 nmol/ml; P < 0.01) as well as a significant decrease in basal GH secretion (1.8 +/- 0.1 vs. 2.5 +/- 0.3 ng/ml; P < 0.05) and a drastic reduction of the GH response to i.v. GH-releasing hormone injection (4.8 +/- 0.7 ng/ml in FFA group vs. 35.8 +/- 9.7 ng/ml in saline group; P < 0.01). No change in plasma insulin-like growth factor I levels was observed. During the first 2 h of infusion, the GH decrease observed was concomitant with a significant increase in portal SRIH levels (22.1 +/- .2 vs. 13 +/- 1.6 pg/ml; P < 0.01). In rams actively immunized against SRIH, the effect of FFA on basal GH secretion was biphasic. During the first 90 min of infusion, the decrease in GH induced by FFA was significantly blunted in rams actively immunized against SRIH (57 +/- 9% for immunized rams vs. 23.5 +/- 2.5% for control rams). This corresponds to the period of increased SRIH portal levels. After this first 90-min period, no difference was seen between control and immunized rams. Our results show that FFA exert their inhibitory action on the GH axis at both pituitary and hypothalamic levels, the latter mainly during the first 90 min, through increased SRIH secretion.
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PMID:Hypothalamic mediated action of free fatty acid on growth hormone secretion in sheep. 983 17

The negative feedback exerted by insulin-like growth factor I (IGF-I) on GH secretion occurs at the pituitary, as well as the hypothalamic level, via stimulation of SS and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) administration inhibits basal GH secretion, at least in fasted humans, though its effect on the GH response to GHRH is still controversial. GH secretagogues (GHS) are peptidyl and nonpeptidyl molecules that act on specific receptors at the pituitary and/or the hypothalamic level. Contrary to GHRH, the GH-releasing activity of GHS is strong, reproducible, and even partially refractory to inhibitory influences such as exogenous somatostatin. We studied the effects of rhIGF-I administration (20 microg/kg s.c. at 0 min) on GH secretion, either spontaneous or stimulated by GHRH (2 microg/kg i.v. at +180 min) or Hexarelin (HEX, 2.0 microg/kg i.v at +180 min), a GHS, in eight normal young women (age, mean +/- SEM, 28.3 +/- 1.2 yr; body mass index, 20.1 +/- 0.5 kg/m2). rhIGF-I administration increased IGF-I levels (peak vs. baseline: 420.3 +/- 30.5 vs. 274.4 +/- 25.3 microg/L, P < 0.05) within the physiological range from +120 to +300 min. No variation in glucose or insulin levels was recorded. rhIGF-I did not reduce spontaneous GH secretion [areas under curves (AUC)(0-300 min) 140.6 +/- 66.3 vs. 114.6 +/- 32.1 microg/L x h], whereas it inhibited the GH response to both GHRH (AUC(180-300 min) 447.7 +/- 159.4 vs. 715.9 +/- 104.3 microg/L x h, P < 0.05) and HEX (620.3 +/- 110.4 vs. 1705.9 +/- 328.9 microg/L x h, P < 0.03). The percent inhibitory effect of rhIGF-I on the GH response to GHRH (41.7 +/- 12.8%) was lower than that on the response to HEX (57.7 +/- 11.0%). In fact, the GH response to GHRH alone was clearly lower than that to HEX alone (P < 0.05), whereas the GH responses to GHRH and HEXwere similar after rhIGF-I. Our findings show that the sc administration of low rhIGF-I doses inhibits the GH response to GHRH and, even more, that to HEX; whereas, at least in this experimental design in fed conditions, it does not modify the spontaneous GH secretion. Because GHS generally show partial refractoriness to inhibitory inputs, including exogenous somatostatin, the present results point toward a peculiar sensitivity of GHS to the negative feedback action of IGF-I.
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PMID:Effects of recombinant human insulin-like growth factor I administration on growth hormone (GH) secretion, both spontaneous and stimulated by GH-releasing hormone or hexarelin, a peptidyl GH secretagogue, in humans. 992 97

To study the hormonal perturbations in FMS patients we injected sixteen FMS patients and seventeen controls a cocktail of the hypothalamic releasing hormones: Corticotropin-releasing hormone (CRH), Thyrotropin-releasing hormone (TRH), Growth hormone-releasing hormone (GHRH), and Luteinizing hormone-releasing hormone (LHRH) and observed the hormonal secretion pattern of the pituitary together with the hormones of the peripheral endocrine glands. We found in FMS patients elevated basal values of ACTH and cortisol, lowered basal values of insulin-like growth factor I (IGF-I) and of triiodothyronine (T3), elevated basal values of follicle-stimulating hormone (FSH) and lowered basal values of estrogen. Following injection of the four releasing-hormones, we found in FMS patients an augmented response of ACTH, a blunted response of TSH, while the prolactin response was exaggerated. The effects of LHRH stimulation were investigated in six FMS patients and six controls and disclosed a significantly blunted response of LH in FMS. We explain the deviations of hormonal secretion in FMS patients as being caused by chronic stress, which, after being perceived and processed by the central nervous system (CNS), activates hypothalamic CRH neurons. CRH, on the one hand, activates the pituitary-adrenal axis, but also stimulates at the hypothalamic level somatostatin secretion which, in turn, causes inhibition of GH and TSH at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH by its ability to inhibit hypothalamic LHRH release, although it could act also directly on the ovary by inhibiting FSH-stimulated estrogen production. We conclude that the observed pattern of hormonal deviations in FMS patients is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.
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PMID:Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones. 1002 90

The aims of this study were (1) to assess possible variations in the serum levels of epidermal growth factor (EGF), insulin-like growth factor I (IGF I) and somatostatin in patients with pancreatic cancer as compared to other pancreatic or extrapancreatic diseases and (2) to ascertain the role of these substances in tumour growth and spread. 35 patients with pancreatic cancer were compared to 15 patients with chronic pancreatitis, 15 with benign hepatobiliary diseases, 23 with benign or malignant gastro-intestinal diseases and 22 control subjects. Increased EGF and IGF I serum levels were found in 10% of patients with pancreatic cancer. Somatostatin levels were increased in 8/16 (50%) patients with pancreatic cancer. No correlation was found between EGF, IGF I or somatostatin and tumour size or stage. In pancreatic cancer somatostatin serum levels were correlated with total bilirubin (p < 0.04), while EGF and IGF I were inversely correlated with fasting serum glucose levels (p < 0.05). In conclusion, (1) the serum levels of EGF, IGF I and somatostatin were not related to tumour size and clinical stage of pancreatic cancer, (2) the serum levels EGF and IGF I may be related to altered glucose metabolism, and (3) liver impairment can influence somatostatin serum levels.
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PMID:Serum growth factors in patients with pancreatic cancer. 1005 Jan 5

Growth hormone (GH) secretion, either spontaneous or evoked by provocative stimuli, is markedly blunted in obesity. In fact obese patients display, compared to normal weight subjects, a reduced half-life, frequency of secretory episodes and daily production rate of the hormone. Furthermore, in these patients GH secretion is impaired in response to all traditional pharmacological stimuli acting at the hypothalamus (insulin-induced hypoglycaemia, arginine, galanin, L-dopa, clonidine, acute glucocorticoid administration) and to direct somatotrope stimulation by exogenous growth hormone releasing hormone (GHRH). Compounds thought to inhibit hypothalamic somatostatin (SRIH) release (pyridostigmine, arginine, galanin, atenolol) consistently improve, though do not normalize, the somatotropin response to GHRH in obesity. The synthetic growth hormone releasing peptides (GHRPs) GHRP-6 and hexarelin elicit in obese patients GH responses greater than those evoked by GHRH, but still lower than those observed in lean subjects. The combined administration of GHRH and GHRP-6 represents the most powerful GH releasing stimulus known in obesity, but once again it is less effective in these patients than in lean subjects. As for the peripheral limb of the GH-insulin-like growth factor I (IGF-I) axis, high free IGF-I, low IGF-binding proteins 1 (IGFBP-1) and 2 (IGFBP-2), normal or high IGFBP-3 and increased GH binding protein (GHBP) circulating levels have been described in obesity. Recent evidence suggests that leptin, the product of adipocyte specific ob gene, exerts a stimulating effect on GH release in rodents; should the same hold true in man, the coexistence of high leptin and low GH serum levels in human obesity would fit in well with the concept of a leptin resistance in this condition. Concerning the influence of metabolic and nutritional factors, an impaired somatotropin response to hypoglycaemia and a failure of glucose load to inhibit spontaneous and stimulated GH release are well documented in obese patients; furthermore, drugs able to block lipolysis and thus to lower serum free fatty acids (NEFA) significantly improve somatotropin secretion in obesity. Caloric restriction and weight loss are followed by the restoration of a normal spontaneous and stimulated GH release. On the whole, hypothalamic, pituitary and peripheral factors appear to be involved in the GH hyposecretion of obesity. A SRIH hypertone, a GHRH deficiency or a functional failure of the somatotrope have been proposed as contributing factors. A lack of the putative endogenous ligand for GHRP receptors is another challenging hypothesis. On the peripheral side, the elevated plasma levels of NEFA and free IGF-I may play a major role. Whatever the cause, the defect of GH secretion in obesity appears to be of secondary, probably adaptive, nature since it is completely reversed by the normalization of body weight. In spite of this, treatment with biosynthetic GH has been shown to improve the body composition and the metabolic efficacy of lean body mass in obese patients undergoing therapeutic severe caloric restriction. GH and conceivably GHRPs might therefore have a place in the therapy of obesity.
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PMID:Growth hormone in obesity. 1019 71

Among other neuropeptides and neurohormones, growth hormone (GH) and somatostatin (SRIF) have been shown to modulate the development of glomerular injury in various renal diseases. In particular, GH is implicated in the induction of glomerular hypertrophy and sclerosis in partial nephrectomy and diabetic nephropathy. While GH effects on glomerular hypertrophy are likely mediated by insulin-like growth factor I (IGF-I), GH effects on glomerular sclerosis are independent of IGF-I. Those effects rather require multiple signaling pathways functioning in series, e.g. angiotensin II binding preceding transforming growth factor beta (TGF-beta) release, or pro-inflammatory factor release preceding repair/scarring processes. In contrast with GH, SRIF administration prevents the development of glomerular lesions in experimental diabetes, partial nephrectomy and immune glomerulonephritis. Inhibitory effects of SRIF on glomerular hypotrophy may be through a decrease in GH secretion and/or IGF-I expression or through a direct blockade of glomerular cell proliferation. The mechanisms underlying the anti-inflammatory effects of SRIF are most likely a deactivation of inflammatory cells related in part to an upregulated response of these cells to glucocorticoids. Additional studies will be required to further define the role of GH and SRIF in the development of glomerular injury and, hence, to identify new targets for a therapeutic approach in glomerular diseases.
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PMID:Growth hormone and somatostatin in glomerular injury. 1020 98

In all species studied to date, growth hormone (GH) is released episodically. Traditionally, the regulation of this process was considered to be mediated by two hypothalamic hormones, growth hormone-releasing hormone (GHRH) and somatostatin (sst). More recently, we identified a new orphan G-protein-coupled receptor that causes episodic GH release upon activation by synthetic ligands. These ligands include the GH-releasing peptides (GHRPs) first described by Bowers and their small molecule mimetics such as L-692,429 and MK-0677. Site-directed mutagenesis of this GH secretagogue receptor (GHS-R) has defined key amino acid residues essential for binding and activation by the synthetic ligands. The GHS-R is not activated by GHRH or sst. It is expressed exclusively in the anterior pituitary lobe and central nervous system and although this new receptor does not belong to any of the known families of G-protein-coupled receptors, the GHS-R is highly conserved across species. The Puffer fish homolog, in common with the human GHS-R, is activated by the structurally distinct ligands GHRP-6, MK-0677 and L-163,540. Thus, the GHS-R ligand-binding pocket has apparently been conserved for at least 400 million years. Studies in humans suggest that production of an endogenous ligand declines during aging. For example, chronic treatment with the synthetic ligand MK-0677 reverses the age-related physiological changes in the GH/IGF-I (insulin-like growth factor I) axis of 70-94 year old subjects. Based on the localization of expression of GHS-R in the brain, reduced production of the natural ligand might also be involved in age-associated changes in cognition, memory, mood and behavior.
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PMID:A New Orphan Receptor Involved in Pulsatile Growth Hormone Release. 1032 6


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