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

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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