BES2003 Poster Presentations Endocrine Tumours and Neoplasia (47 abstracts)
The presence of ghrelin protein in the rat hypothalamus and the effect of ghrelin on corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) release from rat hypothalamic explants pituitary tumours
AM Mozid 1 , G Tringali 2 , ML Forsling 3 , M Hendricks 1 , S Ajodha 1 , R Edwards 1 , P Navarra 2 , AB Grossman 1 & M Korbonits 1
1Department of Endocrinology, St Bartholomew's Hospital, London, UK; 2Department of Pharmacology, Catholic University, Rome, Italy; 3Department of Physiology, UMDS , London, UK.
Ghrelin is a brain-gut peptide originally identified in the stomach. It binds to and stimulates the growth hormone secretagogue receptor type 1a (GHS-R). The presence of ghrelin in hypothalamic tissue was studied. It has been previously established that neither the synthetic GHSs, nor the endogenous hormone ghrelin, is specific for GH stimulation: they generally also stimulate the HPA axis as well as prolactin release. Since there is no direct stimulatory effect on ACTH release from the pituitary, it has been suggested that the secretagogues work via the hypothalamus, on either CRH or AVP or both. The expression of ghrelin mRNA was studied with RT-PCR, ghrelin protein content of rat hypothalamic tissue as well as the ghrelin output of rat hypothalamic explants was studied with a specific ghrelin enzyme immunoassay. The effect of 10-8 to 10-6 M ghrelin on CRH and AVP release was studied in the rat hypothalamic explants, where stimulation with des-ocatnoyl ghrelin was used as control.
Our data showed that ghrelin is expressed in the rat hypothalamus both at the RNA and the protein level. Ghrelin output can be detected in the incubation fluid of rat hypothalamic explants and can be stimulated with high potassium concentration, acting as a nonspecific depolarising stimulus. Our data demonstrated a dose-dependent effect of ghrelin on both CRH and AVP release, while des-octanoylated ghrelin showed no effect on either peptide. However, quantitatively, the effect on AVP was considerably greater (up to a 5-fold stimulation) compared to CRH (1.5-2-fold).
The current data suggest that ghrelin is expressed in the hypothalamus both at the RNA and the protein level. Local autocrine and/or paracrine effects of ghrelin may influence both hormone and appetite regulation in the hypothalamus. The effect of ghrelin on CRH and AVP could either be a direct effect on CRH and AVP neurons in the paraventricular nucleus, or may occur indirectly via NPY.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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