RELATIONSHIP BETWEEN NEUROPEPTIDES AND NITRIC OXIDE IN REGULATING GROWTH HORMONE SECRETION

一氧化氮（NO）是一种新的调节细胞功能的因子。然而，NO在内分泌系统中的作用仍有待阐明。我们曾报道内源性NO通过自分泌和旁分泌调节GH_3细胞生长激素（GH）的分泌。我们还发现，NOS，一种特异性的NO合成酶，存在于垂体GH产生细胞。在正常受试者中，静脉输注TRH而抑制GH分泌，但其机制仍有待澄清。TRH可刺激下丘脑的生长抑素分泌，这反过来又抑制垂体的GH分泌。另外，TRH可刺激垂体中周围促性腺激素细胞释放NO，从而抑制GH产生细胞的GH分泌。另一方面，GH与血管内皮细胞结合，GH可以调节血管内皮细胞NO的产生，NO在下海马的记忆功能中也有重要作用，其中NO的合成受到包括促红细胞生成素（EPO）和胰岛素样生长因子（IGF-I）在内的许多神经肽的调节。我们清楚地阐明了以下机制：1）TRH刺激GH_3细胞产生NO，2）正常大鼠垂体细胞产生NO，3）GH刺激人内皮细胞产生NO，（4）NOS在大鼠海马的分布及EPO和IGF-I对NO产生的刺激作用。提示NO在中枢神经系统中对GH的分泌、作用及记忆功能起重要调节作用。

Nitric oxide(NO) is a new factor to regulate a number of cell functions. However, a role of NO in the endocrine system remains to be elucidated. We previously reported that endogenous NO plays a role in regulating growth hormone(GH) secretion in GH_3 cells as autocrine and paracrine functions. We also found that NOS, a specific synthetase of NO, exists in pituitary GH producing cells. In normal subjects, intravenous infusion of TRH rather inhibited GH secretion although the mechanisms remain to be clarified. TRH may stimulate somatostatin secretion from the hypothalamus, which in turn inhibits GH secretion from the pituitary. Otherwise, TRH may stimulate NO release from surrounding gonadotroph cells in the pituitary, which inhibites GH secretion from GH produsing cells. On the other hand, GH binds to the vasucular endothels in which GH could modify the production of NO. NO also has an important role in the memory function of the hypocampus, in which NO synthesis is regulated by a number of neuropeptides including erythropoietin (EPO) and insulin-like growth factor (IGF-I).In the present study, we clearly elucidated the following mechanisms in which 1)TRH stimulated NO production in GH_3 cells, 2)NO production in the pituitary cells in normal rats, 3)GH stimulated NO production in human endothelial cells, 4)the distribution of NOS and stimulation of NO production by EPO and IGF-I in rat hypocampus. These findings strongly indicate that NO plays an important role in regulating GH secretion, GH action and the memory function in the central nervous system.