Interactions of Growth Hormone Secretagogues with Leptin-Sensitive Brain Networks
| Autor: | Adrian K. Hewson, Loraine Y.C. Tung, S. Lall, J.-O. Jansson, Suzanne L. Dickson |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Chemistry Leptin media_common.quotation_subject digestive oral and skin physiology Growth hormone secretagogue receptor Neuropeptide Appetite Endocrinology Hypothalamus Growth hormone secretagogue Internal medicine medicine Ghrelin Receptor hormones hormone substitutes and hormone antagonists media_common |
| Zdroj: | Research and Perspectives in Endocrine Interactions ISBN: 9783642624001 |
| DOI: | 10.1007/978-3-642-18999-9_1 |
| Popis: | The growth hormone secretagogues (GHS) and ghrelin, an endogenous ligand for the cloned GHS receptor, have recently been shown to induce adiposity in rodents. For some time now, we have been investigating the central site and mechanism of action of GHS, mostly in relation to their growth hormone-releasing action. However, it has become clear that these compounds can activate neuropeptide Y-containing neurones and interact with the hypothalamic circuits controlling body weight and appetite. GHS and ghrelin induce adiposity, although the CNS mechanism underlying this effect may not be fully understood. Hypothalamic circuits regulating body weight can be readily identified as they are responsive to circulating satiety factors such as leptin and insulin. Thus, in electrophysiological studies in vitro we have shown that cells excited by GHS tend to be inhibited by leptin administration. Moreover, GHS-responsive cells appear to be direct targets for leptin, as these responses to GHS and leptin can be observed in a preparation in which synaptic transmission is blocked. Using Fos protein expression to quantify neuronal activation, we have also shown that the hypothalamus is more responsive to GHS/ghrelin in 48-hour fasted rats. This increased responsiveness can be reversed by chronic central infusion of either leptin or insulin. Also refeeding for only two hours at the end of a 48-hour fast reverses the increased responsiveness to GHS, suggesting that central responsiveness to GHS can be regulated acutely, perhaps via some aspect of the feeding process or by absorption of nutrients. We conclude that 1) GHS (and ghrelin) interact with hypothalamic circuits controlling body weight, including leptin- and insulin-sensitive circuits and 2) central responsiveness to GHS is altered by circulating satiety factors and by nutritional state. |
| Databáze: | OpenAIRE |
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