RELATIONSHIP BETWEEN NEUROPEPTIDES AND NITRIC OXIDE IN REGULATING GROWTH HORMONE SECRETION

一氧化氮（NO）是调节多种细胞功能的新因子。然而，一氧化氮在内分泌系统中的作用仍有待阐明。我们之前报道了内源性NO在GH_3细胞中作为自分泌和旁分泌功能调节生长激素（GH）的分泌。我们还发现垂体GH细胞中存在一氧化氮的特异性合成酶NOS。在正常受试者中，静脉输注TRH反而抑制生长激素的分泌，但其机制尚不清楚。TRH可能刺激下丘脑的生长抑素分泌，从而抑制垂体的生长激素分泌。否则，TRH可能刺激垂体周围促性腺细胞释放NO，从而抑制生长激素产生细胞分泌生长激素。另一方面，生长激素与血管内皮结合，可以改变NO的产生。NO在脑下丘脑的记忆功能中也有重要作用，其中NO的合成受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。本研究明确了TRH刺激GH_3细胞NO生成的机制，正常大鼠垂体细胞NO生成的机制，GH刺激人内皮细胞NO生成的机制，EPO和IGF-I刺激NOS在大鼠下丘脑的分布及NO生成的机制。这些结果强烈提示NO在调节中枢神经系统生长激素分泌、生长激素作用和记忆功能中起重要作用。

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.