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

研究了人GH释放激素（hGRF (1-44) -NH_2: hGRF-44）、牛GRF （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、[D-Ala^2, Ala^<15>] -bGRF (1-29) -NH_2）和大鼠GRF （rGRF）在牛体内和体外的GH释放活性。hGRF-44和hGRF (1-29) -NH_2 （hGRF-29）在10^<-14> ~ 10^<-8> M剂量范围内均能显著刺激培养的牛垂体前细胞释放GH （P<0.01）。类似物[D-Ala^2] -hGRF-29在剂量为10^<-18> M至10^<-8> M的培养基中显著诱导GH释放（P<0.01）。bGRF-44、bGRF (1-29) -NH_2 （bGRF-29）和[D-Ala^2， Ala^<15>] -bGRF-29分别在10^<-18>、10^<-17>和10^<-16> M的剂量下显著诱导生长激素释放（P<0.01）。rGRF在10^<-14> ~ 10^<-8> M剂量范围内显著刺激生长激素释放（P<0.01）。这些体外实验结果表明，hGRF、bGRF及其类似物More s和rGRF是牛腺垂体细胞释放生长激素的有效促激素。在体外实验的基础上，研究了bGRF-44、bGRF-29、[D-Ala^2， Ala^<15>] -bGRF-29、[D-Ala^2] -hGRF-29和rGRF对雌性犊牛体内生长激素释放的影响。静脉（iv）单次注射0.25 mug/kg BW的bGRF-44、bGRF-29、[D-Ala^2， Ala^<15>] -bGRF-29、[D-Ala^2] -hGRF-29和rGRF显著刺激GH释放（P<0.05）。注射后60 ~ 120 min， [D-Ala^2, Ala^<15>] -bGRF-29的生长激素响应曲线下面积（AUC）显著（P<0.05）大于bGRF-29或rGRF，注射后120 ~ 180 min， [D-Ala^2, Ala^<15>] -bGRF-29的AUC显著（P<0.05）大于其他肽。在120 ~ 180 min内，[D-Ala^2] -hGRF-29的AUC显著高于bGRF-29 （P<0.05）。这些体内实验结果表明，[D-Ala^2, Ala^<15>] -bGRF-29在雌性小牛体内具有比其他GRF肽更长更强的gh释放活性。本研究明确了各种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分泌剂。少

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