| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
1.We found that under experimental conditions where hypothalamic GHRH expression is increased, e.g.GH deficiency due to GH gene mutation, glucocorticoid deficiency and hypothyroidism, we observed that pituitary ghrelin expression was also increased. The pituitary ghrelin was also found to be decreased in conditions where hypothalamic GHRH expression is decreased, e.g.GH treatment, glucocorticoids excess, hyperthyroid state and food deprivation. Collectively, these results suggest that pituitary ghrelin expression is GHRH-dependent.
2.We also conducted functional studies to examine if the pituitary ghrelin/GHS-R system contributes to GH release after GHRH stimulation, by challenging pituitary cell cultures with GHRH in the presence of a GHS-R specific inhibitor. The GHS-R inhibitor did not affect GH release in the absence of GHRH, but significantly reduced GHRH-mediated GH release. These indicated that endogenous pituitary ghrelin can play a physiological role in GH release, by optimizin
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g somatotroph responsiveness to GHRH.
3.We examined the direct effects of insulin, leptin, and glucagon on the release of ghrelin from the isolated rat stomach. Insulin and leptin inhibited ghrelin secretion dose dependently, while glucagon increased it dose dependently. These results indicate that the ghrelin responses observed in vivo could be due to direct effects of multiple hormonal signals on the stomach.
4.To investigate the hyperphagic response to thyrotoxicosis, T3-treated rats were examined. Plasma leptin levels were markedly decreased. However, the expression of the ghrelin gene in the stomach and plasma ghrelin concentrations did not diffe. Therefore, the decreased plasma leptin levels could contribute to the hyperphagia in T3-induced thyrotoxicosis. However, plasma ghrelin levels could not contribute to this hyperphagia.
5.The effects of IGF-I on the GHSR gene expression and on the GH response to GHS in rat pituitary cell cultures were examined. Pituitary GHS-R mRNA levels were decreased in a dose and time-dependent manner by IGF-I. The GH response to the receptor ligand was significantly reduced by pretreatment with IGF-I. Thus IGF-I could inhibit GH secretion at least in part by regulating the expression of the GHS-R Less
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