Studies on the development of high potent growth hormone (GH) -releasing hormone analogs in inducing the release of bovine GH.

开发高效生长激素（GH）释放激素类似物诱导牛 GH 释放的研究。

• 批准号: 07660369
• 负责人: HASHIZUME Tsutomu
• 金额: $ 1.41万
• 依托单位: Iwate University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07660369/
• 关键词: GH; Growth hormone; GRF; GHRH; Growth hormone-releasing hormone; cattle

The growth hormone (GH) -releasing activity of human GH-releasing hormone (hGRF (1-44) -NH_2 : hGRF-44), bovine GRF (bGRF (1-44) -NH_2 : bGRF-44) and their analogs (hGRF (1-29) -NH_2, [D-Ala^2] -hGRF (1-29) -NH_2, bGRF (1-29) -NH_2, [D-Ala^2, Ala^<15>] -bGRF (1-29) -NH_2) as well as rat GRF (rGRF) were examined in vitro and in vivo in cattle. Both of the hGRF-44 and hGRF (1-29) -NH_2 (hGRF-29) significantly stimulated GH release from cultured bovine anterior pituitary cells at doses from 10^<-14> to 10^<-8> M (P<0.01). The analog [D-Ala^2] -hGRF-29 significantly induced GH release in media at doses from 10^<-18> to 10^<-8> M (P<0.01). The bGRF-44, bGRF (1-29) -NH_2 (bGRF-29) and [D-Ala^2, Ala^<15>] -bGRF-29 significantly induced GH release in media at doses as low as 10^<-18>,10^<-17>, and 10^<-16> M,respectively (P<0.01). The rGRF significantly stimulated GH release at doses ranging from 10^<-14> to 10^<-8> M (P<0.01). These in vitro results suggest that the hGRF,bGRF and their analog … More s, as well as rGRF,are potent secretagogues of GH release from adenohypophysial cells in cattle. Following the in vitro experiments, the effects of bGRF-44, bGRF-29, [D-Ala^2, Ala^<15>] -bGRF-29, [D-Ala^2] -hGRF-29, and rGRF on the release of GH were studied in vivo in female calves. The intravenous (iv) single injection of 0.25 mug/kg BW of bGRF-44, bGRF-29, [D-Ala^2, Ala^<15>] -bGRF-29, [D-Ala^2] -hGRF-29, and rGRF significantly (P<0.05) stimulated GH release. The area under GH response curve (AUC) obtained from [D-Ala^2, Ala^<15>] -bGRF-29 was significantly (P<0.05) greater than those obtained from bGRF-29 or rGRF in 60-120 min after the injections, and the AUC in the [D-Ala^2, Ala^<15>] -bGRF-29 was significantly (P<0.05) greater than those obtained from the other peptides in 120-180 min after the injections. The AUC obtained from [D-Ala^2] -hGRF-29 was significantly (P<0.05) greater than that obtained from bGRF-29 in the 120-180 min. From these in vivo results show that [D-Ala^2, Ala^<15>] -bGRF-29 has longer and greater GH-releasing activity than the other GRF peptides in female calves. The present study clarified the GH-releasing activity of various GRFs, and demonstrated that the [D-Ala^2, Ala^<15>] -bGRF-29 is the most potent GH secretagogue in the GRFs in cattle. Less

本文研究了人生长激素释放激素（hGRF（1-44）-NH_2：hGRF-44）、牛生长激素释放激素（bGRF（1-44）-NH_2：bGRF-44）及其类似物（hGRF（1-29）-NH_2、[D-Ala^2] -hGRF（1 - 29）-NH_2、bGRF（1 - 29）-NH_2、[D-Ala^2，Ala^<15>2] -bGRF（1-29）-NH_2）和大鼠生长激素释放激素（rGRF）的体外和体内生长激素释放活性。hGRF-44和hGRF（1-29）-NH_2（hGRF-29）在10 μ M ~ 10 μ M浓度范围内均能显著促进牛垂体前叶细胞生长激素的释放<-14><-8>（P&lt;0.01）。类似物[D-Ala^2] -hGRF-29在10 μ M至10 μ M的剂量下显著诱导培养基中的GH释放<-18><-8>（P&lt;0.01）。bGRF-44、bGRF（1-29）-NH_2（bGRF-29）和[D-Ala^2，Ala^<15>] -bGRF-29分别在低至10 μ M<-18>、10 μ <-17>M和10 μ <-16>M的剂量下显著诱导培养基中GH的释放（P&lt;0.01）。rGRF在10 μ M ~ 10 μ M范围内显著刺激GH释放<-14><-8>（P&lt;0.01）。这些体外结果表明，hGRF、bGRF及其类似物 ...更多信息 s和rGRF是牛腺垂体细胞释放GH的有效促分泌素。在体外实验之后，在雌性小牛体内研究bGRF-44、bGRF-29、[D-Ala^2，Ala^<15>2] -bGRF-29、[D-Ala^2] -hGRF-29和rGRF对GH释放的影响。单次静脉注射0.25 μ g/kg BW的bGRF-44、bGRF-29、[D-Ala^2，Ala^3<15>] -bGRF-29、[D-Ala^2] -hGRF-29和rGRF显著刺激GH释放（P&lt;0.05）。注射后60-120 min内，[D-Ala^2，Ala^ ] -bGRF-29的GH响应曲线下面积（AUC）<15>显著（P&lt;0.05）大于bGRF-29或rGRF，注射后120- 180 min内，[D-Ala^2，Ala^<15>] -bGRF-29的AUC显著（P&lt;0.05）大于其他肽的AUC。在120-180分钟内，[D-Ala^2] -hGRF-29获得的AUC显着（P&lt;0.05）大于bGRF-29获得的AUC。这些体内结果表明，[D-Ala^2，Ala^<15>] -bGRF-29在雌性小牛中具有比其他GRF肽更长和更大的GH释放活性。本研究阐明了各种GRF的GH释放活性，并证明[D-Ala^2，Ala^<15>] -bGRF-29是牛GRF中最有效的GH促分泌剂。少

项目成果

E.B.Soliman, T.Hashizume, S.Ohashi, S.Kanematsu: "Effects of growth (GH) -releasing hormone and its analogs on GH secretion from cultured adenohypophysial cells in cattle." Domestic Anim.Endocrinol.14. 39-46 (1997)

E.B.Soliman、T.Hashizume、S.Ohashi、S.Kanematsu：“生长 (GH) 释放激素及其类似物对牛培养的腺垂体细胞 GH 分泌的影响。”

E. B. Sollman, T. Hashizume, S. Ohashi, S. Kenematsu: "Effects of growth (GH)-releasing hormone and its analogs on GH secretion from cultured adenohypophysial cells in cattle." Domestic Anim. Endocrinol.14. 39-46 (1997)

E. B. Sollman、T. Hashizume、S. Ohashi、S. Kenematsu：“生长 (GH) 释放激素及其类似物对牛培养的腺垂体细胞 GH 分泌的影响。”

T. Hashizume, K. Sasaki, M. Sakai, S. Tauchi, H. Masuda: "The effect of new growth hormone-releasing peptide (KP102) on the release of growth hormone in goats." Anim. Scl. Thechnol. (Jpn.). (印刷中). (1997)

T. Hashizume、K. Sasaki、M. Sakai、S. Tauchi、H. Masuda：“新型生长激素释放肽 (KP102) 对山羊生长激素释放的影响。”日本）（正在出版）（1997）。