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      Adrenocorticotropin/cortisol and arginine-vasopressin secretory patterns in response to ghrelin in normal men.

      Neuroendocrinology
      Adrenocorticotropic Hormone, blood, Adult, Arginine Vasopressin, Ghrelin, Humans, Hydrocortisone, Male, Peptide Hormones, pharmacology, Radioimmunoassay, methods, Statistics as Topic, Time Factors

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          Abstract

          This study was performed in order to establish the secretory patterns and the possible relationships between the adrenocorticotropin (ACTH)/cortisol and arginine vasopressin (AVP) responses in normal men to the systemic administration of ghrelin, an endogenous ligand for the growth hormone secretagogue receptor. For this purpose, a bolus of 1 microg/kg ghrelin was injected intravenously in 9 normal men. AVP, ACTH and cortisol significantly rose in response to ghrelin injection; however, in all subjects the AVP rise preceded the ACTH/cortisol responses. In fact, the mean peak levels of AVP, ACTH and cortisol after ghrelin injection were observed at 15, 30 and 45 min, respectively. When peak AVP responses to ghrelin were considered together with ACTH and cortisol peak levels, highly significant positive correlations were observed (AVP and ACTH, r = 0.94, p < 0.001; AVP and cortisol, r = 0.92, p < 0.001). In conclusion, this study shows that the AVP response to ghrelin precedes the concomitant ACTH/cortisol rise and that these hormonal responses are highly positively correlated. These observations support the hypothesis that AVP mediates ghrelin-induced ACTH secretion in normal men. Copyright 2005 S. Karger AG, Basel

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          Most cited references12

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          A receptor in pituitary and hypothalamus that functions in growth hormone release.

          Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone.
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            Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues

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              Ghrelin is released from rat hypothalamic explants and stimulates corticotrophin-releasing hormone and arginine-vasopressin.

              Ghrelin and synthetic growth hormone secretagogues have diverse effects on the hypothalamus including effects on appetite and the growth hormone axis as well as on the hypothalamus-pituitary-adrenal (HPA) axis. We previously studied the effect of synthetic growth hormone secretagogues on CRH and AVP release from rat hypothalami in vitro, and now report on the effects of ghrelin on CRH and AVP release. The ghrelin protein content and ghrelin output from rat hypothalamic explants was measured using a specific novel ghrelin enzyme immunoassay. The effect of 10(-8) M to 10(-6) M ghrelin on CRH and AVP release was studied in the rat hypothalamic explants, where stimulation with des-octanoyl ghrelin was used as control. The presence of both ghrelin mRNA and protein could be shown in the rat hypothalamus. Ghrelin output was detected in the incubation fluid of rat hypothalamic explants and could be stimulated with high potassium concentrations. Our data also demonstrated a dose-dependent effect of ghrelin on both CRH and AVP release, while des-octanoylated ghrelin showed no effect on either peptide. In summary, the current data suggest that ghrelin is expressed in the hypothalamus both at RNA and the protein levels. Ghrelin stimulates the HPA axis in the rat via stimulation of both CRH, and particularly, AVP release from the hypothalamus. The local autocrine/paracrine and endocrine effects of ghrelin in the hypothalamus could influence all the hormonal systems involved in ghrelin effects, including growth hormone release, the HPA axis and appetite.
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