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

生长抑素（SS）可抑制内分泌和外分泌组织中多种激素的释放，在中枢神经系统中可能起神经调质的作用。SS最初与SS受体结合。SS受体在某些内分泌疾病和脑功能障碍中表达异常，但其表达调控机制尚不清楚。本研究的目的是寻找调节垂体和神经元样细胞SS受体表达的内源性因子，阐明E_2对垂体细胞SS受体表达的作用机制，并探讨脑发育早期大脑皮质SS受体瞬时表达的生理意义。结果表明：（1）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受体均为E_2非依赖型。(2)E_2上调GH_3细胞SS和TRH受体。注射GH_3细胞mRNA的非洲爪蟾卵母细胞中，虽然未检测到SS受体，但观察到TRH受体的功能性表达。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。结果发现NS 20 Y和Neuro 2A细胞具有SS受体（SS_A亚型）。因此，它们为研究通过分化调节受体提供了合适的模型。在体外分化过程中，用二甲基亚砜、前列腺素E_1或神经节苷脂处理可使生长抑素受体的结合数减少。这些结果表明，在垂体前叶SS受体的表达上调外周激素和下调时，神经元样细胞分化。

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.