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Basic and Clinical Studies of Regulatory Mechanism of GH Secretion

GH分泌调节机制的基础与临床研究

基本信息

批准号：
62570524
负责人：
SHIBASAKI Tamotsu
金额：
$ 1.34万
依托单位：
Tokyo Women's Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570524/
关键词：
Growth hormone Growth hormone releasing factor Somatostatin Insulin tolerance test Arginine 分泌調節

项目摘要

Several provocative tests for GH secretion such as insulin tolerance, 1-dopa, arginine infusion and GRF tests have been used in clinical endocrinology. However, the precise mechanisms of GH secretion are not clear in these tests. The mechanisms were, therefore, investigated in this study. Intravenous (iv) injection of 200ug GRF or 0.1U/kg b.w. regular insulin, oral administration of 500mg 1-dopa or infusion of 30g arginine for 30min was preformed 120min, 120min, 90min, or 105nin, respectively, after iv administration of 200ug GRF. The effect of prior subcutaneous administration of SMS201-995, a long acting somatostatin analog, on GH secretion in each provocative test was examined in the same manner. The secretion of GH in response to 200ug GRF was completely inhibited by the prior administration of 200ug GRF, whereas that induced by insulin, 1-dopa or arginine was not affected by the prior sdministration of GRF. The secretion of GH induced by 1-dopa or arginine was completely inhibited by the prior administration of 50ug SMS201-995, and that induced by GRF was completely inhibited by 100ug SMS201-995. The response of GH secretion to insulin was small but significantly preserved even after administration of 100ug SMS201-995. Taken together with the previous reports that 1-dops elevates plasma GRF levels and arginine has no influence on plasma GRF levels, it is suggested that 1-dops stimulates GH secretion probably by suppression of somatostatin release in addition to stimulation of GRF and that arginine stimulates GH secrtion probably by suppression of somatostatin release. It is also suggested that some factor (s) other than GRF and somatostatin is involved in the mechanism whereby insulin stimulates GH secretion since the effect of insulin still exists in the presence of exogenous GRF or somatostatin.

几种刺激GH分泌的试验，如胰岛素耐量试验、1-多巴试验、精氨酸输注试验和GRF试验已用于临床内分泌学。然而，GH分泌的确切机制在这些试验中尚不清楚。因此，在本研究中研究了其机制。静脉注射200 ug GRF或0.1 U/kg b.w.静脉注射GRF 200 μ g后，分别于120 min、120 min、90 min、105 min给予常规胰岛素、1-多巴500 mg口服或精氨酸30 g静滴30 min。以相同的方式检查预先皮下施用SMS 201 -995（一种长效生长抑素类似物）对每次激发试验中GH分泌的影响。预先给予200 μ gGRF可完全抑制200 μ gGRF诱导的GH分泌，而预先给予GRF对胰岛素、1-多巴和精氨酸诱导的GH分泌无影响。预先给予50 μ g SMS 201 -995可完全抑制1-多巴或精氨酸诱导的GH分泌，预先给予100 μ g SMS 201 -995可完全抑制GRF诱导的GH分泌。GH分泌对胰岛素的反应很小，但即使在100 ug SMS 201 -995给药后也显著保持。结合文献报道的1-dops可提高血浆GRF水平，而精氨酸对血浆GRF水平无影响，提示1-dops刺激GH分泌可能除刺激GRF外，还通过抑制生长抑素释放，精氨酸刺激GH分泌可能通过抑制生长抑素释放。提示胰岛素刺激GH分泌的机制可能与GRF和生长抑素以外的其他因素有关，因为在存在外源性GRF或生长抑素的情况下，胰岛素的作用仍然存在。