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

生长抑素（Somatostatin， SS）抑制内分泌和外分泌组织中各种激素的释放，可能在中枢神经系统中起神经调节剂的作用。SS最初与SS受体结合。SS受体的异常表达在一些内分泌疾病和脑功能障碍中是已知的，但其表达的调控机制尚不清楚。本研究旨在寻找调节垂体和神经元样细胞中SS受体的内源性因子，阐明E_2对垂体细胞中SS受体表达的作用机制，并研究大脑发育早期大脑皮层瞬时表达的生理意义。结果是；(l)甲状腺激素和聚adp核糖合成酶抑制剂协同提高SS受体的结合活性。这些药物诱导的SS受体为e_2独立亚型。(2) E_2上调GH_3细胞的SS和TRH受体。GH_3细胞MRNA注射后，在爪蟾卵母细胞中观察到TRH受体的功能表达，而SS受体未见表达。E_2增加TRH受体MRNA活性。(3)神经母细胞瘤培养细胞具有神经元的许多特性。我们发现NS20Y和Neuro 2A细胞具有SS受体（SS_A亚型）。因此，它们为研究受体的分化调控提供了一个合适的模型。在体外分化中，二甲亚砜、PGE_1或神经节苷脂处理可降低生长抑素受体的结合数量。这些结果表明，SS受体的表达在垂体前叶受到外周激素的上调，并在神经元样细胞分化时下调。

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.