Hodate K, Johke T, Ohashi S
Endocrinol Jpn. 1986 Aug;33(4):519-25. doi: 10.1507/endocrj1954.33.519.
Responses of growth hormone (GH) release to synthetic human growth hormone-releasing factor (hGRF)-44-NH2 analogs were determined, and the GH-releasing potency based on dose per kg of body weight (bw) was compared with that of hGRF-44-NH2 in female dairy calves. Four- and 12-month-old calves were injected intravenously with 0.25 microgram of hGRF-44-NH2 or its analogs per kg of bw. Blood samples were collected before, and during 180 min after each injection, and plasma GH concentrations were measured by radioimmunoassay. Areas under the GH response curves for 180 min after injection of hGRF-44-NH2 and its analogs were used as an index of the GH-releasing potency of each peptide. The GH-releasing potency of hGRF(1-26)-NH2 was significantly lower than that of hGRF-44-NH2 (P less than 0.05). On the other hand, hGRF(1-29)-NH2 possessed similar potency to hGRF-44-NH2. [D-Tyr1]-hGRF-44-NH2 showed prolonged GH-releasing activity, though its potency was similar to that of hGRF-44-NH2. Also, [D-Ala2]-hGRF(1-29)-NH2 exhibited prolonged GH-releasing activity, and its potency was 2.5 (P less than 0.05) and twice (P less than 0.05) as great as that of hGRF-44-NH2 and hGRF(1-29)-NH2, respectively. These results demonstrate that the N-terminal 29 amino acid residues of hGRF possess the activity site required for full GH release in vivo, and [D-Ala2]-hGRF(1-29)-NH2 has longer and greater activity, on a dose basis, than hGRF-44-NH2 in the calves.
测定了生长激素(GH)释放对合成的人生长激素释放因子(hGRF)-44-NH₂类似物的反应,并在雌性犊牛中比较了基于每千克体重(bw)剂量的GH释放效力与hGRF-44-NH₂的效力。给4月龄和12月龄的犊牛静脉注射每千克体重0.25微克的hGRF-44-NH₂或其类似物。在每次注射前及注射后180分钟内采集血样,通过放射免疫测定法测定血浆GH浓度。注射hGRF-44-NH₂及其类似物后180分钟的GH反应曲线下面积用作每种肽的GH释放效力指标。hGRF(1-26)-NH₂的GH释放效力显著低于hGRF-44-NH₂(P<0.05)。另一方面,hGRF(1-29)-NH₂具有与hGRF-44-NH₂相似的效力。[D-Tyr¹]-hGRF-44-NH₂显示出延长的GH释放活性,尽管其效力与hGRF-44-NH₂相似。此外,[D-Ala²]-hGRF(1-29)-NH₂表现出延长的GH释放活性,其效力分别比hGRF-44-NH₂和hGRF(1-29)-NH₂高2.5倍(P<0.05)和两倍(P<0.05)。这些结果表明,hGRF的N端29个氨基酸残基具有体内完全释放GH所需的活性位点,并且在犊牛中,基于剂量,[D-Ala²]-hGRF(1-29)-NH₂比hGRF-44-NH₂具有更长和更强的活性。