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)

Public health efforts and current antiobesity agents have not controlled the increasing epidemic of obesity. Investigational antiobesity agents consist of 1) central nervous system agents that affect neurotransmitters or neural ion channels, including antidepressants (bupropion), selective serotonin 2c receptor agonists, antiseizure agents (topiramate, zonisamide), some dopamine antagonists, and cannabinoid-1 receptor antagonists (rimonabant); 2) leptin/insulin/central nervous system pathway agents, including leptin analogues, leptin transport and/or leptin receptor promoters, ciliary neurotrophic factor (Axokine), neuropeptide Y and agouti-related peptide antagonists, proopiomelanocortin and cocaine and amphetamine regulated transcript promoters, alpha-melanocyte-stimulating hormone analogues, melanocortin-4 receptor agonists, and agents that affect insulin metabolism/activity, which include protein-tyrosine phosphatase-1B inhibitors, peroxisome proliferator activated receptor-gamma receptor antagonists, short-acting bromocriptine (ergoset), somatostatin agonists (octreotide), and adiponectin; 3) gastrointestinal-neural pathway agents, including those that increase cholecystokinin activity, increase glucagon-like peptide-1 activity (extendin 4, liraglutide, dipeptidyl peptidase IV inhibitors), and increase protein YY3-36 activity and those that decrease ghrelin activity, as well as amylin analogues (pramlintide); 4) agents that may increase resting metabolic rate ("selective" beta-3 stimulators/agonist, uncoupling protein homologues, and thyroid receptor agonists); and 5) other more diverse agents, including melanin concentrating hormone antagonists, phytostanol analogues, functional oils, P57, amylase inhibitors, growth hormone fragments, synthetic analogues of dehydroepiandrosterone sulfate, antagonists of adipocyte 11B-hydroxysteroid dehydrogenase type 1 activity, corticotropin-releasing hormone agonists, inhibitors of fatty acid synthesis, carboxypeptidase inhibitors, indanones/indanols, aminosterols, and other gastrointestinal lipase inhibitors (ATL962). Finally, an emerging concept is that the development of antiobesity agents must not only reduce fat mass (adiposity) but must also correct fat dysfunction (adiposopathy).
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PMID:Current and investigational antiobesity agents and obesity therapeutic treatment targets. 1534 Jan

Obesity is associated with different disturbances in endocrine function. Both spontaneous growth hormone (GH) secretion and its response to several stimuli have shown to be reduced in obese patients. The GH responses to GH-releasing hormone and other challenges by pyridostigmine suggest that the reduction in GH secretion is related to an increased somatostatinergic tone. Other experiments point to a down-regulation of somatostatin receptors in the somatotroph cell. Ghrelin administration is followed by a massive GH release, but the possibility that ghrelin or GHRH deficiency are the cause of GH deficiency in obesity is unlikely. The increase in free fatty acids in obesity might be related to GH reduction, since acipimox administration is able to reverse GH secretion. In women, abdominal obesity is associated with hyperandrogenism and low sex hormone-binding globulin levels. Obese men have low testosterone and gonadotrophin concentrations, specially in cases of morbid obesity. An increase in hypothalamic-pituitary-adrenal axis activity and some resistance to dexamethasone suppression have been described in abdominal obesity. This effect may be due to neuroendocrine alterations related to a genetic origin. Adrenal hyperfunction may favour cardiovascular and metabolic complications. There are no disturbances in thyroid function. Sometimes a reduction in prolactin response to several stimuli has been reported. This effect may be due to hyperinsulinaemia or to disturbances in the dopaminergic tone.
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PMID:[Neuroendocrine disturbances in obesity]. 1538 10

Prion diseases are believed to develop from the conformational change of normal cellular prion protein (PrPc) to a pathogenic isoform (PrPsc). PrPc is present in both the central nervous system and many peripheral tissues, although protein concentration is significantly lower in non-neuronal tissues. PrPc expression is essential for internalization and replication of the infectious agent. Several works have pointed to the gastrointestinal (GI) tract as the principal site of entry of PrPsc, but how passage through the GI mucosa occurs is not yet known. Here we studied PrPc expression using Western blot, RT-PCR, and immunohistochemistry in rat GI tract. PrPc mRNA and protein were detected in corpus, antrum, duodenum, and colon. Immunoreactivity was found in scattered cells of the GI epithelium. With double immunofluorescence, these cells have been identified as neuroendocrine cells. PrPc immunostaining was found in subsets of histamine, somatostatin (Som), ghrelin, gastrin (G), and serotonin (5HT) cells in stomach. In small and large bowel, PrPc cells co-localized with subpopulations of 5HT-, Som-, G-, and peptide YY-immunolabeled cells. Our results provide evidence for a possible and important role of endocrine cells in the internalization of PrPsc from gut lumen.
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PMID:Cellular prion protein is expressed in a subset of neuroendocrine cells of the rat gastrointestinal tract. 1538 82

Growth hormone (GH) is secreted in a pulsatile manner, but the underlying mechanisms of GH pulse generation remain to be resolved. In the present study, we investigated the relationship between GH pulses in the peripheral circulation and GH-releasing hormone (GHRH) and somatostatin (SRIF) profiles in the cerebrospinal fluid (CSF) of male goats. The effects of an intracerebroventricular (icv) injection of neuropeptide Y (NPY), galanin and ghrelin were also analyzed. Blood and CSF samples were collected every 15 min for 8 hr from the jugular vein and third ventricle, respectively. GH pulsatility in the goat was found to consist of distinct large pulses of 5 hr periodicity and small pulses of 1 hr periodicity. GHRH and SRIF in the CSF fluctuated in a pulsatile manner with 1 hr periodicity, and most of the descending phase of SRIF pulses were associated with the initiation of GH pulses. Icv injections of NPY, galanin and ghrelin stimulated GHRH release without affecting SRIF release. In addition, NPY suppressed, and galanin and ghrelin induced large GH pulses, although ghrelin was much more effective than galanin. These results suggest that an hourly fall in SRIF is involved in generating intrinsic circhoral rhythm of GH pulsatility. The mechanisms underlying the generation of large GH pulses of 5 hr periodicity remain unknown, while direct action of NPY and/or ghrelin on the pituitary might be involved.
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PMID:Relationship between growth hormone (GH) pulses in the peripheral circulation and GH-releasing hormone and somatostatin profiles in the cerebrospinal fluid of goats. 1547 70

Ghrelin, a specific endogenous ligand for the GH secretagogue receptor, stimulates GH secretion in humans when given in pharmacological amounts. Under physiological conditions, however, it is controversial whether ghrelin affects GH secretion and vice versa. No studies have reported on the relationship between daily ghrelin and GH secretion in children. Therefore, plasma ghrelin and GH concentrations over a 24-h period were studied in 10 prepubertal short normal children (five females and five males) to determine the potential relationship between the secretion of these two hormones. Furthermore, five prepubertal patients (two females and three males) with GH neurosecretory dysfunction (GHNSD) were studied in the same way to assess potential alterations in ghrelin secretion in a condition associated with distinct GH changes. No gender difference in ghrelin spontaneous secretion was detected in either short normal children or GHNSD patients, and in both male and female subjects, ghrelin was secreted in a pulsatile and circadian fashion, with a nocturnal surge. Twenty-four-hour secretion and daytime ghrelin secretion of short normal children were similar to those in GHNSD patients, whereas nighttime hormone secretion in the latter group was significantly greater than that in short normal children. The cross-correlation of 24-h ghrelin and GH levels revealed significant positive and negative correlations, which were similar in the two groups examined. The positive one, with GH leading ghrelin, might reflect a somatostatin (SMS)-mediated inhibitory effect on both GH and ghrelin secretion (low SMS levels are followed by high GH and ghrelin levels, and vice versa). The negative correlation, with ghrelin leading GH, might again reflect the positive effect of ghrelin on SMS, as shown in both animal and human studies. In conclusion, the results of the present study indicate that ghrelin secretion in prepubertal children is pulsatile and is not sexually dimorphic. Although the parallelism of ghrelin and GH dynamics hints at the potential relevance of endogenous ghrelin as a promoter of GH release, our data do not support this hypothesis. We suggest that the interactions of ghrelin and GH are the result of SMS action. SMS inhibits GH secretion not only by a direct effect on the pituitary and by inhibiting hypothalamic GHRH, but also through the suppression of ghrelin release.
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PMID:Spontaneous growth hormone (GH) secretion is not directly affected by ghrelin in either short normal prepubertal children or children with GH neurosecretory dysfunction. 1553 2

Several neuropeptides affect the sleep-wake cycle, for example, vasoactive intestinal polypeptide, cholecystokinin octapeptide, orexin, somatostatin, insulin, leptin, ghrelin, neuropeptide Y and cortistatin, which regulate food ingestion. There are also proteins from the immunological system: tumor necrosis factor-alpha, interleukin (IL)-1beta IL-4, IL-10, IL-13, as well as trophic molecules, such as growth hormone-releasing hormone, growth hormone, prolactin, brain-derived neurotrophic factor and nerve growth factor, neurotrophin-3 and neurotrophin-4. Based on this information, we believe that some functions of sleep can be suggested. One of these functions could be the regulation of energy, since many, if not all, of the neuropeptides that regulate feeding affect the level of alertness. Likewise, the immunological system and the trophic molecules establish a dialog with the brain during sleep in order to reestablish neuronal structure. These proteins are the expression of genes that accomplish the function of regulating our waking and our sleep, suggesting the important control the genome is exerting on this activity.
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PMID:The role of neuropeptides in sleep modulation. 1560 11

Release of growth hormone (GH) is known to be regulated mainly by GH-releasing hormone (GHRH) and somatostatin (SRIF) secreted from the hypothalamus. A novel peripheral release-regulating hormone, ghrelin, was recently identified. In this study, differences of the GH secretory response to ghrelin and GHRH in growing and lactating dairy cattle were investigated and an alteration of plasma ghrelin levels was observed. The same amounts of ghrelin and GHRH (0.3 nmol/kg) were intravenously injected to suckling and weanling calves, early and mid-lactating cows and non-lactating cows. Plasma ghrelin levels were also determined in dairy cattle in various physiological conditions. The peak values of ghrelin-induced GH secretion were increased in early lactating cows compared to those in non-lactating cows. The relative responsiveness of GH secretion to ghrelin was also increased compared with that to GHRH in early lactating cows. GH secretory responses to GHRH were blunted in mature cows with and without lactation. Conversely, GHRH-induced GH secretory response was greater than that to ghrelin in calves, and also greater in calves than in mature cows. Plasma ghrelin concentrations were elevated in early lactating cows compared to those in non-lactating cows. Plasma GH concentrations were higher in suckling calves and early lactating cows compared with those in non-lactating cows. These results suggest that GHRH is an effective inducer of GH release in growing calves, and that the relative importance of ghrelin in contributing to the rise in plasma GH increases in early lactating cows.
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PMID:GH secretory responses to ghrelin and GHRH in growing and lactating dairy cattle. 1562 Aug 5

The present study examines the thesis that pulsatile GH secretion is controlled simultaneously by three principal signals; viz., GHRH, GH-releasing peptide (GHRP, ghrelin), and somatostatin (SS). According to this ensemble notion, no single regulatory peptide acts alone or can be interpreted in isolation. Therefore, to investigate gender-specific control of pulsatile GH secretion, we designed dual-effector stimulation paradigms in eight young men and six women as follows: 1) L-arginine/GHRH (to clamp low SS and high GHRH input); 2) L-arginine/GHRP-2 (to clamp low SS and high GHRP drive); 3) GHRH/GHRP-2 (to clamp high GHRH and high GHRP feedforward); vs. 4) saline (unclamped). Statistical comparisons revealed that: 1) fasting pulsatile GH secretion was 7.6-fold higher in women than men (P < 0.001); 2) L-arginine/GHRH and L-arginine/GHRP-2 evoked, respectively, 4.6- and 2.2-fold greater burst-like GH release in women than men (P < 0.001 and P = 0.015); and 3) GHRH/GHRP-2 elicited comparable GH secretion by gender. In the combined cohorts, estradiol concentrations positively predicted responses to L-arginine/GHRP-2 (r2= 0.49, P = 0.005), whereas testosterone negatively predicted those to L-arginine/GHRH (r2= 0.56, P = 0.002). Based upon a simplified biomathematical model of three-peptide control, the current outcomes suggest that women maintain greater GHRH potency, GHRP efficacy, and opposing SS outflow than men. This inference upholds recent clinical precedence and yields valid predictions of sex differences in self-renewable GH pulsatility.
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PMID:Complementary secretagogue pairs unmask prominent gender-related contrasts in mechanisms of growth hormone pulse renewal in young adults. 1563 14

Both growth hormone (GH)/insulin growth factor (IGF)-1 axis and energy balance have been implicated in longevity independently. The aim of the present study was to characterize the effect of a 72-h fasting period at 3 months of age in four different rat strains: (i) Wistar and (ii) Fischer 344 rats, which develop obesity with age, and (iii) Brown Norway and (iv) Lou C rats, which do not. Wistar rats ate more, were significantly bigger, and presented with higher plasma leptin and lower ghrelin levels and hypothalamic growth hormone-releasing hormone (GHRH) content than rats from the three other strains. Plasma insulin and IGF-1 levels were lower in Brown Norway and Lou C rats, and somatostatin content was lower in Brown Norway rats only. Glycaemia was lower in Lou C rats that displayed a lower relative food intake compared to Fischer and Wistar rats. Brown Norway rats showed a greater caloric efficiency than the three other strains. Concerning major hypothalamic neuropeptides implicated in feeding, similar amounts were detected in the four strains for neuropeptide Y, agouti-related peptide, galanin, melanin-concentrating hormone, alpha-melanocortin-stimulating hormone (alpha-MSH) and corticotropin-releasing hormone. Orexin A appeared to be slightly elevated in Fischer rats and cocaine amphetamine-regulated transcript (CART)(55-102) diminished in Brown Norway. At the mRNA level, orexin A, GHSR1, alpha-MSH and CART expression were higher in Wistar and Lou C rats. Principal component analysis confirmed the presence of two main factors in the ad libitum rat population; the first being associated with growth-related parameters and the second being associated with food intake regulation. Hypothalamic GHRH and somatostatin content were positively correlated with feeding-related neuropeptides such as alpha-MSH for GHRH, and orexin A and CART for both peptides. Plasma ghrelin levels were negatively correlated with leptin and IGF-1 levels. Finally, a 72-h fasting period affected minimally body weight, plasma IGF-1 and leptin levels in Lou C rats compared to the three other strains, and plasma insulin levels were less affected in Brown Norway rats. In conclusion, Wistar shorter life span is consistent with its already fatter phenotype at 3 months of age. In terms of IGF-1, glycaemia and leptin responses to fasting, the Lou strain, which presents with a low food intake/body weight and caloric efficiency, is the least affected. The link between food intake regulation, GH axis and ageing is further demonstrated by principal component analysis, where GHRH and somatostatin were found to be strongly associated with energy homeostasis parameters.
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PMID:Plasma and hypothalamic peptide-hormone levels regulating somatotroph function and energy balance in fed and fasted states: a comparative study in four strains of rats. 1566 53

Ghrelin is a native ligand for the growth hormone secretagogue (GHS) receptor that stimulates pulsatile GH secretion markedly. At present, no formal construct exists to unify ensemble effects of ghrelin, GH-releasing hormone (GHRH), somatostatin (SRIF), and GH feedback. To model such interactions, we have assumed that ghrelin can stimulate pituitary GH secretion directly, antagonize inhibition of pituitary GH release by SRIF, oppose suppression of GHRH neurons in the arcuate nucleus (ArC) by SRIF, and induce GHRH secretion from ArC. The dynamics of such connectivity yield self-renewable GH pulse patterns mirroring those in the adult male and female rat and explicate the following key experimental observations. 1) Constant GHS infusion stimulates pulsatile GH secretion. 2) GHS and GHRH display synergy in vivo. 3) A systemic pulse of GHS stimulates GH secretion in the female rat at any time and in the male more during a spontaneous peak than during a trough. 4) Transgenetic silencing of the neuronal GHS receptor blunts GH pulses in the female. 5) Intracerebroventricular administration of GHS induces GH secretion. The minimal construct of GHS-GHRH-SRIF-GH interactions should aid in integrating physiological data, testing regulatory hypotheses, and forecasting innovative experiments.
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PMID:Deterministic construct of amplifying actions of ghrelin on pulsatile growth hormone secretion. 1571 92


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