Preferred Label : Food Intake and Energy Homeostasis Pathway;
NCIt related terms : Ghrelin: Regulation of Food Intake and Energy Homeostasis;
Alternative definition : BIOCARTA: The synthesis and release of growth hormone (GH) from the pituitary are
controlled by the hypothalamic hormones GH-releasing hormone (GHRH) and somatostatin
(SRIF), which in turn are regulated by feedback from blood GH and insulin-like growth
factor-I (IGF-I) concentrations. The recently discovered endogenous GH-releasing peptide,
called ghrelin, also stimulates GH release. Circulating GH acts directly on many organs
to stimulate IGF-I production, with IGF-I production in the liver providing the main
source of blood IGF-I. Most of the IGF-I in the circulation is bound to IGF-binding
protein-3 (IGFBP-3) in a ternary complex with acid-labile subunit (ALS); a smaller
fraction is bound to the five other IGFBP. A small fraction of the total IGF-I in
blood is in a bioactive-free fraction. In the kidney, IGF-I increases renal plasma
flow and GFR, whereas on bone it acts on the epiphysial plate, which leads to longitudinal
bone growth. GH also has direct effects on many organs, including kidney and cartilage,
which can be independent of IGF-I action. The GH/IGF-I axis in chronic renal failure
(CRF) is changed markedly compared with the normal axis. In CRF, the total concentrations
of the hormones in the GH/IGF-I axis are not reduced, but there is reduced effectiveness
of endogenous GH and IGF-I, which probably plays a major role in reducing linear bone
growth. The reduced effectiveness of endogenous IGF-I likely is due to decreased levels
of free, bioactive IGF-I as levels of circulating inhibitory IGFBP are increased.
In addition, less IGF-I is circulating in the complex with ALS and IGFBP-3 as a result
of increased proteolysis of IGFBP-3. Together, these lead to decreased IGF-I receptor
activation and a decreased feedback to the hypothalamus and pituitary. Low free IGF-I
and high IGFBP-1 and -2 levels probably contribute to a reduced renal function and
lead to a reduced stature. The direct effects of GH on bone, which are poorly understood,
also are blunted. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_ghrelinPathway;
Origin ID : C39093;
UMLS CUI : C1517287;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
