1991 Fiscal Year Final Research Report Summary
On-off regulation of hypothalamic GRF secretion by somatostatin
| Project/Area Number |
02671110
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
MIKI Nobuhiro Tokyo Women's Medical College Dept. of Med. Assistant professor, 医学部, 講師 (40157467)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Masami Tokyo Women's Medical College Dept. of Med. Assistant professor, 医学部, 助手 (90152537)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Growth hormone / Growth hormonereleasing factor / Somatostatin / Hypothalamus / Pituitary / 下垂体 |
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| Research Abstract |
Somatostatin (SRIF) is a tetradecapeptide originally isolated as a hypothalamic hypophysiotropic growth hormone (GH)-inhibiting factor. In 1988, we demonstrated that sudden withdrawal of endogenous SRIF induced secretion of GH-releasing factor (GRF) in vivo and suggested that SRIF acts as a GRF-inhibiting factor within the hypothalamus. Our research project, supported by a Grant-in-Aid 1990-1991, was to extend this novel concept of our own. For this porupose, we have-established the method of rat hypothalamic incubation. We have also developed culture system of isolated nerve endings of the stalk-median eminence and the perifusion system of rat hypothalami. GRF and SRIF were measured by highly specific RIAs. To deplete SRIF, we used a thiol agent cysteamine and a gamma-globulin fraction separated from rabbit SRIF antiserum by Protein A-Sepharose. An addition of cysteamine to the medium stimulated basal GRF secretion and enhanced K^+-evoked GRF secretion from incubated hypothalami in a concentration- and Ca^<2+>-dependent manner. GRF secreted into the medium was characterized by Sep-Pak C18 and reverse-phase HPLC. We have also demonstrated that SRIF inhibition of GRF secretion is absent in an early neonatal period and develops approximately 7-10 days after birth, which correspond the time when the hypophysial portal vessels are established in the rat. This finding supports physiological significance of the on off regulation of GRF secretion by SRIF. Furthermore, we have observed that an addition of anti-SRIF gamma-globulin to the medium augments GRF release from hypothalamic synaptosomes and that a periodicinfusion of cysteamine can stimulate GRF secretion from perifused rat hypothalami. Collectively, these findings support the concept that SRIF acts as a GRF-inhibiting factor at the level of the hypothalamus.
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