1991 Fiscal Year Final Research Report Summary
Regulatory mechanism of expression of somatostatin receptors in the anterior pituitary and the cerebral cortex.
| Project/Area Number |
02670074
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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 |
環境生理学(含体力医学･栄養生理学)
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| Research Institution | Tokyo Metropolitan Institute for Neurosciences |
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Principal Investigator |
KIMURA Nobuko Tokyo Metropolitan Institute for Neurosciences, 分子神経生物学研究部門, 主任研究員 (70100138)
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| Project Period (FY) |
1990 – 1991
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| Keywords | somatostatin-receptor / pituitary-cultured-cells / estrogen / thyroid-hormone / TRH receptor / neuroblastoma / differentiation |
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| Research Abstract |
Somatostatin (SS) inhibits the release of various hormones in endocrine and exocrine tissues, and may act as a neuromodulator in the central nervous system. SS acts initially to bind to the SS receptors. Abnormal expression of SS receptor is known in some endocrine diseases and brain dysfunction, but the regulatory mechanism of the receptor expression remains to be elucidated. The aim of this study is to find endogenous factors which regulate SS receptor in the pituitary and neurone-like cells, to elucidate the action mechanism of E_2 on the receptor expression in the pituitary cells, and to study phisiological significant of the transient expression in early stage of brain development in the cerebral cortex. The results were ; (l) Thyroid hormone and poly (ADP-ribose) syntheiase inhibitors synergistically increased the binding activity of SS receptors. The SS receptor induced by these drugs was E_2-independent subtype. (2) E_2 up-regulates both SS and TRH receptors in GH_3 cells. Functional expression of TRH receptors was observed in Xenopus oocytes injected with MRNA from GH_3 cells, although SS receptors was not detected. E_2 increased MRNA activity of TRH receptor. (3) Neuroblastoma cultured cells have many properties of neurones. We found that NS20Y and Neuro 2A cells possessed SS receptors (SS_A subtype). And so, they provide a suitable model for the study of regulation of receptors by differentiation. In vitro differentiation by the treatment with dimethyl sulfoxide, PGE_1 or gangliosides decreased the binding number of somatostatin receptors. These results demonstrate that the expression of SS receptors is up-regulated by peripheral hormones in the anterior pituitary and down-regulated when neurone-like cells are differentiated.
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