RELATIONSHIP BETWEEN NEUROPEPTIDES AND NITRIC OXIDE IN REGULATING GROWTH HORMONE SECRETION

一氧化氮(NO)是一种调节多种细胞功能的新因子。然而，NO在内分泌系统中的作用仍有待阐明。我们先前报道内源性NO通过自分泌和旁分泌功能调节GH_3细胞生长激素(GH)的分泌。我们还发现，一氧化氮合酶是一种特异性的NO合成酶，存在于垂体生长激素产生细胞中。在正常受试者中，静脉输注TRH相当于抑制GH的分泌，尽管其机制尚不清楚。TRH可以刺激下丘脑的生长抑素分泌，而下丘脑的生长抑素又会抑制脑下垂体的生长激素分泌。否则，TRH可能会刺激周围的垂体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可调节NO的产生。NO在下丘脑的记忆功能中也起着重要的作用，在下丘脑中，NO的合成受促红细胞生成素(EPO)和胰岛素样生长因子(IGF-I)等神经肽的调节。在本研究中，我们明确地阐明了TRH刺激GH_3细胞产生NO，2)正常大鼠脑垂体细胞产生NO，3)GH刺激人内皮细胞产生NO，4)NOS的分布以及EPO和IGF-I刺激大鼠下丘脑产生NO的机制。这些结果有力地表明，NO在调节中枢神经系统的GH分泌、GH作用和记忆功能方面起着重要作用。

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.