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)

Growth hormone-releasing peptides (GHRPs) are synthetic molecules with strong, dose-related and reproducible growth hormone (GH)-releasing activity in humans. GHRPs act at both the pituitary and the hypothalamic level, where specific receptors have been located. In adults, GHRPs release more GH than does GH-releasing hormone (GHRP), whilst their co-administration has a synergistic effect, indicating that they have, at least partially, different mechanisms of action. However, normal activity of GHRH-secreting neurones is needed to achieve the full GH-releasing effect of GHRPs. In contrast to GHRH, the GH-releasing activity of GHRPs is not further increased by substances acting via inhibition of hypothalamic somatostatin, and is only blunted by substances that stimulate hypothalamic somatostatin release. Even free fatty acids and exogenous somatostatin, which act directly on somatotrophs, do no more than blunt the effect of GHRPs. Thus, the GH-releasing activity of GHRPs is partially refractory to inhibitory influences, GHRPs act, at least in part, by antagonism of somatostatin activity, both at the pituitary and the hypothalamic level. The GH-releasing effect of GHRPs is not dependent on gender, but undergoes age-related variations. Gonadal steroids seem to influence the activity of GHRPs only in childhood. The reduced GH response to GHRPs in the elderly is probably due mainly to concomitant GHRH hypoactivity and somatostatinergic hyperactivity. A preserved GH-releasing effect of GHRPs has been reported in acromegaly, anorexia nervosa, hyperthyroidism and in critically ill patients. GHRPs have also been found to increase GH release in children with idiopathic short stature, in GH deficiency and in obese patients, in whom there is a well-known reduction of somatotroph function. The GH response to GHRPs is markedly reduced in hypothyroidism and Cushing's syndrome.
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PMID:Age-related growth hormone-releasing activity of growth hormone secretagogues in humans. 940 52

Growth hormone-releasing peptides (GHRPs) are a series of hepta (GHRP-1)- and hexapeptides (GHRP-2, GHRP-6, Hexarelin) that have been shown to be effective releasers of GH in animals and humans. More recently, a series of nonpeptidyl GH secretagogues (L-692,429, L-692,585, MK-0677) were discovered using GHRP-6 as a template. Some cyclic peptides as well as penta-, tetra-, and pseudotripeptides have also been described. This review summarizes recent developments in our understanding of the GHRPs, as well as the current nonpeptide pharmacologic analogs. GHRPs and their analogs have no structural homology with GHRH and act via specific receptors present at either the pituitary or the hypothalamic level. The GHRP receptor has recently been cloned and it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. Although the exact mechanism of action of GHRPs has not been fully established, there is probably a dual site of action on both the pituitary and the hypothalamus, possibly involving regulatory factors in addition to GHRH and somatostatin. Moreover, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. The marked GH-releasing activity of GHRPs is reproducible and dose-related after intravenous, subcutaneous, intranasal, and even oral administration. The GH-releasing effect of GHRPs is the same in both sexes, but undergoes age-related variations. It increases from birth to puberty and decreases in aging. The GH-releasing activity of GHRPs is synergistic with that of GHRH and not affected by opioid receptor antagonists, while it is only blunted by inhibitory influences that are known to nearly abolish the effect of GHRH, such as neurotransmitters, glucose, free fatty acids, glucocorticoids, rhGH, and even exogenous somatostatin. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states, such as acromegaly, anorexia nervosa, and hyperthyroidism. On the other hand, GHRPs and their analogs have been reported to be effective in idiopathic short stature, in some situations of GH deficiency, in obesity, and in hypothyroidism, while in patients with pituitary stalk disconnection and in Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. A potential role in the treatment of short stature, aging, catabolic states, and dilated cardiomyopathy has been envisaged.
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PMID:Growth hormone-releasing peptides and their analogs. 946 89

Since the time of Freud, psychiatry has embraced the proposition that physiological and/or psychological stress precipitates various psychiatric disorders. To this effect, we propose that a continuum of liability obtains between stress, anxiety states and anorexia nervosa--a continuum which is grounded on a cytokine profile common to each of these conditions. For example, the biological response to stress, anxiety states and anorexia nervosa includes the elevation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), and downregulation of interferon-gamma (IFN-gamma). Sustained elevation of IL-1 beta and TNF-alpha dysregulates both somatostatin and insulin secretion, the latter of which influences regional cerebral blood flow (rCBF) and brain energy metabolism. In addition, IL-1 beta and TNF-alpha influence the expression of certain crucial neuropeptides, which are known to be associated with anxiety states and anorexia nervosa. These neuropeptides include: beta-endorphin, cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). beta-endorphin effects glucose metabolism in the limbic system, CCK increases the release of beta-endorphin from the anterior pituitary, NPY is a powerful anxiolytic that regulates beta-endorphin and insulin, while VIP indirectly regulates the expression of TNF-alpha through the inhibition of interleukin-4 (IL-4).
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PMID:Tumor necrosis factor-alpha: is there a continuum of liability between stress, anxiety states and anorexia nervosa? 1034 Feb 96

Galanin (GAL) elicits growth hormone (GH) release in normal subjects through interaction with hypothalamic somatostatin. GAL also stimulates GH-releasing hormone (GHRH) secretion in vitro. In rats, GAL is able to stimulate prolactin (PRL) release, but this effect is not clear in humans. We have thus investigated GAL effects on GH and PRL release in patients with anorexia nervosa (AN), known to have altered regulation of the GH-insulin-like growth factor axis and PRL dynamics, and compared the effects of GHRH and GAL on GH and PRL secretion in AN and normal healthy subjects. Eight women with AN (15 to 27 years; body mass index [BMI], 17 to 19.5 kg/m2) were treated with (1) GHRH 50 microg intravenous (IV) injection, (2) porcine GAL 500 microg infusion from -10 to +30 minutes, and (3) 135-minutes saline infusion as a control, respectively. Both peptides induced a significant increase in plasma GH in AN patients (peak level, 27.41 +/- 5.50 microg/L after GAL and 18.97 +/- 2.67 microg/L after GHRH). When data for AN patients and the control group were compared, GH peak levels after GAL were significantly higher in AN patients (27.41 +/- 5.50 v 13.64 +/- 2.32 microg/L), while GH peak levels after GHRH were not different between the 2 groups (18.97 +/- 2.67 v 15.98 +/- 3.88 microg/L). PRL levels significantly increased after both GHRH (peak, 11.70 +/- 2.80 microg/L) and GAL (peak, 18.02 +/- 5.10 microg/L) treatment in AN patients, but not in normal subjects. We conclude that GAL stimulates exaggerated GH release in AN patients as compared with normal controls, suggesting a dual hypothalamic interaction via both an increase in endogenous GHRH and a decrease in somatostatin secretion. Finally, GAL may act as a PRL secretagogue in AN patients.
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PMID:Effects of galanin on growth hormone and prolactin secretion in anorexia nervosa. 1069 Sep 37

To evaluate the neuroendocrinological dysfunction in anorexia nervosa, plasma somatostatin, glucose, insulin, and growth hormone were monitored in ten patients with anorexia nervosa in the active and refeeding (remission) phases of the disorder and in nine age-matched healthy control subjects. Somatostatin levels were significantly higher in the anorectic patients in both the active and refeeding phases than in the controls at baseline (mean+/-SD 27.4 +/-5.5 and 31.1+/-2.6 vs 21.3+/-1.9 pg/ml; p<0.001), and significantly higher in the anorectic patients in the active phase compared to the refeeding phase and to the controls in response to a mixed meal (p<0.05). Insulin levels were significantly lower in the anorectic patients in both the active and refeeding phases compared to the controls at baseline (9.3+/-1.1, 7.6+/-1.0 vs 14.7+/-3.5 microU/ml; p<0.0001) and after a mixed meal (p<0.05). An attenuated glucose response discriminated the anorectic patients in the active state from the same patients in the refeeding state and the controls (p<0.0001). There was no significant difference in growth hormone response between the anorectic patients and the controls. These findings suggest that there is an augmented response of somatostatin and an attenuated response of insulin to mixed meal stimulation in active anorexia. The diminished insulin response persists during the refeeding phase. It seems that central and peripheral alterations in endocrine function occur in anorexia nervosa.
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PMID:Neuroendocrinological response to standardized mixed meal in female anorectic patients during active and refeeding phases. 1071 66

Two fundamentally different methods are currently used for the determination of free insulin-like growth factor-I (IGF-I): ultrafiltration by centrifugation (UF) and direct immunoradiometric assay (IRMA). The aim was to evaluate a commercial IRMA (DSL, Webster, TX, USA) and to compare it with UF. In the IRMA it is recommended that samples be incubated for 2 h at 5;C. When comparing samples (n = 8) incubated for 1 and 2 h, levels increased by 27 +/- 5% (P< 0.0001). When incubating samples at 22;C instead of 5;C, levels increased by 192 +/- 32% (P< 0.0001). Addition of IGF-binding protein-1 (IGFBP-1) to normal sera (n = 6) dose-dependently decreased ultrafiltered free IGF-I only (P< 0.0007). Similarly, UF was more sensitive than IRMA to addition of IGFBP-2 (P< 0.05). In healthy subjects (n = 35) IRMA yielded 20% higher levels than UF (1.09 +/- 0.09 vs 0.91 +/- 0.12 microg/L; P< 0.0001). IRMA and UF yielded similar results in healthy subjects treated with IGF-I (n = 5) or growth hormone (n = 7) and in acromegalic patients (n = 6) before and after somatostatin analogue treatment. However, marked differences were observed in conditions with elevated IGFBP-1 and -2. In type-1 diabetics (n = 23) ultrafiltered free IGF-I was more reduced than IRMA free IGF-I (38 +/- 9 vs 76 +/- 7% of matched controls (n = 13); P< 0.0001). In patients with chronic renal failure (n = 25), IRMA free IGF-I was identical to control levels (n = 13), whereas ultrafiltered free IGF-I was decreased by 51 +/- 7% (P< 0.0001). Similarly, women with anorexia nervosa (n = 9) studied before and after weight gain showed significant changes in ultrafiltered free IGF-I only (P< 0.03). In conclusion, IRMA was not very robust with respect to variations in sample incubation and this may bias results. IRMA generally yielded higher levels than UF, in accordance with the knowledge that IRMA measures free plus readily dissociable IGF-I. IRMA was less affected than UF by added IGFBP-1 and -2, and reductions in free IGF-I were better revealed by UF than IRMA.
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PMID:Determination of free insulin-like growth factor-I in human serum: comparison of ultrafiltration and direct immunoradiometric assay. 1147 78

A few examples of hypothalamic, peptidergic disorders leading to clinical signs and symptoms are presented in this review. Increased activity of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) and decreased activity of the vasopressin neurons in the biological clock and of the thyroxine-releasing hormone (TRH) neurons in the PVN contribute to the signs and symptoms of depression. In men, the central nucleus of the bed nucleus of the stria terminalis (BSTc) is about twice as large and contains twice as many somatostatin neurons as in women. In transsexuals this sex difference is reversed, pointing to a role of this structure in gender. Luteinizing hormone-releasing hormone (LHRH) neurons are formed in the fetal olfactory placade and migrate along the terminal nerve fibers into the hypothalamus. In Kallmann's syndrome the migration process of the LHRH (gonadotropin-releasing hormone) neurons is aborted, which explains the joint occurrence of hypogonadotropic hypogonadism and anosmia in this syndrome. In postmenopausal women, the neurons of the infundibular nucleus hypertrophy and become hyperactive because of the disappearance of the estrogen feedback and contain hyperactive peptidergic neurons. Climacteric flushes may be caused by hyperactivity of the neurokinin-B or LHRH neurons in this nucleus. The hypocretin (orexin) neurons in the perifornical area are involved in sleep. In narcolepsy with cataplexy, a loss of these neurons, probably due to an autoimmune process, is found. Obese subjects with a mutation in the gene that encodes for leptin, the preproghrelin gene, or the alpha-melanocyte-stimulating hormone (alpha-MSH) gene have been described. Decreased numbers and activity of the oxytocin neurons in the PVN may be responsible for the absence of satiety in Prader-Willi syndrome. Moreover, a glucocorticoid receptor polymorphism is associated with obesitas and dysregulation of the hypothalamus-pituitary-adrenal axis. In contrast, two single nucleotide polymorphisms (SNPs) of the AGRP gene have been associated with anorexia nervosa.
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PMID:Neuropeptides in hypothalamic neuronal disorders. 1554 16

Patients with anorexia nervosa (AN) may develop multiple endocrine abnormalities, including amenorrhea, hyperactivity of the hypothalamus-pituitary-adrenal axis, hypothyroidism and particular changes in the activity of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. Exaggerated GH secretion and reduced IGF-I levels are usually found in AN, as well as in conditions of malnutrition and malabsorption, insulin-dependent diabetes mellitus, liver cirrhosis and catabolic states. In AN, GH hypersecretion at least partially reflects malnutrition-induced peripheral GH resistance, which leads to reduced IGF-I synthesis and release; this implies an impairment of the negative IGF-I feedback action on GH secretion. On the other hand, primary alterations in the neural control of GH secretion cannot be ruled out. The neuroendocrine alterations include enhanced somatotroph responsiveness to growth hormone releasing hormone (GHRH) and impaired GH response to most central nervous system-mediated stimuli. Particular resistance to cholinergic manipulation has also been demonstrated, thus suggesting a somewhat specific alteration in the somatostatin (SS)-mediated cholinergic influence on GH secretion. Moreover, paradoxical GH responses to glucose load, thyrotropin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) have also been reported. The effect of reduced leptin levels on GH hypersecretion in AN is still unclear, but ghrelin (the gastric hormone that is a natural ligand of the GH secretagogue receptor and strongly stimulates somatotroph secretion) is thought to play a major role. Regardless of the supposed central and peripheral alterations, it has to be emphasised that the activity of the GH/IGF-I axis in AN is generally restored by nutritional and stable weight gain. It therefore reflects an impaired nutritional state and cannot be considered a primary hallmark of the disease.
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PMID:GH/IGF-I axis in anorexia nervosa. 1764 63


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