INT144356

Context Info Confidence 0.57 First Reported 2007 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 4 Total Number 26 Disease Relevance 10.76 Pain Relevance 2.21

Anatomy Link Frequency pituitary 3 fat 2 pancreatic islets 1 chondrocytes 1 alpha cells 1 GHS (Homo sapiens)

Pain Link Frequency Relevance Heat Dopamine 46 98.56 medulla 92 98.00 agonist 391 96.40 Somatostatin 167 95.08 Inflammation 230 95.04 Opioid 1 94.00 antagonist 439 93.72 narcan 1 93.28 Eae 69 92.52 ischemia 46 92.28

Disease Link Frequency Relevance Heat Targeted Disruption 391 99.96 Growth Problems 115 99.50 Hypoglycemia 92 96.40 Renal Failure 92 96.16 INFLAMMATION 276 95.04 Aging 102 94.96 Insulin Resistance 116 94.68 Disease 26 94.52 Obesity 347 93.68 Pancreatic Cancer 23 93.36

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Above all, ghrelin and synthetic GHS possess an acute stimulatory effect on the activity of the hypothalamus-pituitary-adrenal axis in humans, which is, at least, similar to that of the opioid antagonist naloxone, arginine vasopressin and even corticotropin-releasing hormone.

Gene_expression (synthetic) of GHS in pituitary associated with antagonist, narcan and opioid

1) Confidence 0.57 Published 2010 Journal Front Horm Res Section Abstract Doc Link 20616513 Disease Relevance 0 Pain Relevance 0.23

RESULTS: GHS was present in 52 patients (48.6%) and correlated significantly to shoulder pain at TI, at T2 and at T3 (p < 0.001).

Gene_expression (present) of GHS in shoulder

2) Confidence 0.52 Published 2007 Journal Physiother Res Int Section Body Doc Link 17536647 Disease Relevance 0.16 Pain Relevance 0

Long-term surveillance of ghrelin and GHS receptor-deficient and ghrelin-overexpressing transgenic animals will be needed to assess whether prolonged changes in ghrelin availability influence immune function or inflammatory disease. 5.11.

Gene_expression (overexpressing) of GHS associated with targeted disruption, inflammation and disease

3) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 1.87 Pain Relevance 0.32

Conversely, in a fourth model, transgenic reduction of GHS-R1a expression on GHRH neurons suppressed both GHRH and NPY gene expression, thereby diminishing GH and fat mass in the female [236].

Gene_expression (expression) of GHS in fat associated with targeted disruption

4) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.67 Pain Relevance 0.05

Ghrelin, GHS receptors, GH, and GH receptors are expressed in human monocytes and B and T lymphocytes [576].

Gene_expression (expressed) of GHS in T lymphocytes

5) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.85 Pain Relevance 0.08

GHS receptors are expressed by both beta and alpha cells [442].

Gene_expression (expressed) of GHS in alpha cells

6) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.12 Pain Relevance 0.07

Mutational disruption of constitutive GHS-R1a activity is associated with short stature in humans [27], whereas overexpression of GHS-R1a on GHRH neurons augments postweaning growth, reduces fat mass, and augments GHRH and GH gene expression in mice [28].

Gene_expression (overexpression) of GHS in neurons associated with growth problems

7) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.17 Pain Relevance 0.07

Adult pancreatic islets express relatively little ghrelin protein and few GHS receptors, but fetal and neonatal islets exhibit abundant ghrelin gene transcripts and peptide in epsilon cells [452–454].

Gene_expression (express) of GHS in pancreatic islets

8) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.85 Pain Relevance 0.10

Conversely, overexpression of neuronal GHS-R1a in female mice elevates GH and GHRH gene expression [28].

Gene_expression (overexpression) of GHS in neuronal

9) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.19 Pain Relevance 0.04

Although physiological effects are not clear, ghrelin is expressed in sheep oocytes [634], and GHS-R1a in Sertoli (nurse) cells in spermatogenic tubules [623].

Gene_expression (expressed) of GHS in tubules

10) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.46 Pain Relevance 0.04

In a third model, overexpression of GHS-R1a in GHRH neurons increased organ and muscle weight, while decreasing body fat in female animals [28].

Gene_expression (overexpression) of GHS in body

11) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.63 Pain Relevance 0

The dorsal motor nucleus of the vagus expresses GHS-R1a, which modulates limbic-system dopamine- and brainstem gaba, glutamine, and noradrenergic transmission to hypothalamic appetitive and satiety centers [335, 341–343].

Gene_expression (expresses) of GHS in brainstem associated with medulla and dopamine

12) Confidence 0.30 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.08 Pain Relevance 0.37

Reduced pituitary action of SS is unlikely to be the sole potentiating mechanism subserving GHS action, since GHS and GHRH synergize even after immunoneutralization of SS [268].

Gene_expression (synergize) of GHS in pituitary

13) Confidence 0.26 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.11 Pain Relevance 0.04

Although local acylation could explain certain actions of unacylated ghrelin, other effects that oppose or differ from those of acylated peptide raise the possibility of non-GHS-R1a mediation.

Gene_expression (mediation) of GHS

14) Confidence 0.26 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.32 Pain Relevance 0.13

An endogenous ligand for the GHS receptor, acylghrelin, was identified in 1999.

Gene_expression (receptor) of GHS

15) Confidence 0.26 Published 2010 Journal International Journal of Peptides Section Abstract Doc Link PMC2925380 Disease Relevance 0.11 Pain Relevance 0

Thus, GHS-R1a is an amplifier of GHRH outflow as well as a direct effector of pituitary GH secretion.

Gene_expression (outflow) of GHS in pituitary

16) Confidence 0.26 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.15 Pain Relevance 0.08

Figure 2 depicts a model, which incorporates several major actions of ghrelin/GHS within the GH axis [41].

Gene_expression (actions) of GHS

17) Confidence 0.26 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.12 Pain Relevance 0.09

Unlike ghrelin, synthetic GHS's acting via GHS-R1a typically do not require acylation and are not known GOAT substrates.

Gene_expression (synthetic) of GHS

18) Confidence 0.26 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.88 Pain Relevance 0.16

In addition, prolonged administration of ghrelin or synthetic GHS in humans augments GH, IGF-I and IGFBP-3 concentrations and lean-body mass, and diminishes total-body fat, while eliciting transient secretion of adenocorticotropin hormone (ACTH), cortisol, and prolactin [64, 269–273].

Gene_expression (synthetic) of GHS in fat

19) Confidence 0.26 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.18 Pain Relevance 0.04

The basis may involve pregnancy-associated suppression of hypothalamic GHRH and GHS-R1a with reciprocal induction of the SS gene due to feedback by high placental somatomammotropin (GH isotype V) and maternal IGF-I concentrations [422].

Gene_expression (suppression) of GHS

20) Confidence 0.26 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.24 Pain Relevance 0

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