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Regulatory mechanism of expression of somatostatin receptors in the anterior pituitary and the cerebral cortex.

垂体前叶和大脑皮层生长抑素受体表达的调节机制。

基本信息

批准号：
02670074
负责人：
KIMURA Nobuko
金额：
$ 0.9万
依托单位：
Tokyo Metropolitan Institute for Neurosciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

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.

生长抑素（SS）抑制内分泌和外分泌组织中各种激素的释放，并可能充当中枢神经系统的神经调节剂。 SS 最初的作用是与 SS 受体结合。 SS受体的异常表达已知在一些内分泌疾病和脑功能障碍中，但受体表达的调节机制仍有待阐明。本研究的目的是寻找调节垂体和神经元样细胞SS受体的内源性因子，阐明E_2对垂体细胞受体表达的作用机制，并研究大脑皮层大脑发育早期瞬时表达的生理学意义。结果是； (l)甲状腺激素和聚(ADP-核糖)合成酶抑制剂协同增加SS受体的结合活性。这些药物诱导的SS受体是E_2非依赖性亚型。 (2) E_2上调GH_3细胞中的SS和TRH受体。尽管未检测到 SS 受体，但在注射 GH_3 细胞 mRNA 的非洲爪蟾卵母细胞中观察到 TRH 受体的功能性表达。 E_2增加了TRH受体的mRNA活性。 (3)神经母细胞瘤培养的细胞具有许多神经元的特性。我们发现 NS20Y 和 Neuro 2A 细胞拥有 SS 受体（SS_A 亚型）。因此，它们为研究分化调节受体提供了合适的模型。用二甲亚砜、PGE_1或神经节苷脂处理进行的体外分化降低了生长抑素受体的结合数量。这些结果表明，SS受体的表达受到垂体前叶外周激素的上调，而在神经元样细胞分化时下调。