Harvey S, Gineste C, Gaylinn B D
Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Department of Chemistry, University of Virginia, Charlottesville, VA 22908, USA.
Gen Comp Endocrinol. 2014 Aug 1;204:261-6. doi: 10.1016/j.ygcen.2014.06.007. Epub 2014 Jun 20.
Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor.
通过对鸡基因组的分析，已鉴定出两种与生长激素释放激素（GHRH）具有序列相似性的肽。其中一种肽，鸡（c）GHRH-LP（类肽），先前发现它与鸡垂体膜或克隆并表达的鸡GHRH受体结合不佳，并且在体内或体外几乎没有生长激素（GH）释放活性。相比之下，最近发现的第二种肽，cGHRH，确实能与克隆并表达的cGHRH受体结合，并增加转染细胞中的cAMP活性。因此，评估了这种肽可能具有体内GH释放活性的可能性。以3-100μg/kg的剂量对未成熟鸡静脉内（i.v.）注射cGHRH，在注射后10分钟内显著增加了循环GH浓度，并且在注射最大有效剂量后，血浆GH水平至少升高30分钟。血浆GH对cGHRH的反应与人类（h）或猪（p）GHRH制剂诱导的反应以及促甲状腺激素释放激素（TRH）诱导的反应相当。与之形成鲜明对比的是，静脉注射cGHRH-LP对未成熟雏鸡的循环GH浓度没有显著影响。用0.1μg/ml或1.0μg/ml的cGHRH对屠宰场鸡垂体进行5分钟的灌流，也能增加GH释放，这与GH对hGHRH1-44的反应相当。相比之下，用cGHRH-LP对鸡垂体进行灌流对GH释放没有显著影响。总之，这些结果表明cGHRH在鸡中具有GH释放活性，并支持它是cGHRH受体的内源性配体的可能性。
