Studies on novel growth hormone (GH) secretory mechanisms by ghrelin in ruminants

Ghrelin是一种新型的内源性生长激素（GH）促分泌剂，已被证明在大鼠和人类中发挥非常有效和特异性的GH释放活性。然而，对其在家畜体内的gh释放活性和内分泌作用知之甚少。为了阐明胃饥饿素对反刍动物生长激素分泌的影响，我们在山羊和牛体内和体外研究了胃饥饿素对生长激素的释放作用。比较了人胃饥饿素（hGhrelin）和大鼠胃饥饿素（rGhrelin）在体外对牛垂体前叶（AP）细胞的gh释放作用和gh释放激素（GHRH）的作用。hGhrelin和rGhrelin分别在10^<-10> M至10^<-7> M和10^<-9>至10^<-7> M剂量范围内显著刺激培养细胞的生长激素释放（P<0.05）。然而，ghrelin的gh释放作用弱于GHRH。当hGhrelin （10^<-8>M）和GHRH （10^<-8>M）同时加入时，两种肽诱导的GH释放量均显著大于单独使用hGhrelin (P<0.0…More 5)，且有大于单独使用GHRH的趋势。生长抑素（SS, 10^<-7> M）显著抑制生长素（10^<-8>M）和GHRH （10^<-8>M）诱导的生长激素释放（P<0.05）。在SS存在的情况下，hGhrelin和GHRH对GH的释放有叠加效应（P<0.05）。牛的体外实验结果与猪相似。为了阐明胃饥饿素对反刍动物体内生长激素分泌的影响，研究了山羊和牛动脉和下丘脑注射胃饥饿素后血浆生长激素的反应。去卵巢山羊动脉下注射3 μg/kg BW的rGhrelin显著提高了血浆GH浓度（P<0.05）。3 μg/kg BW的rGhrelin的分泌反应弱于0.25μg/kg BW的GHRH。向下丘脑内侧基底核（弓状核）注入10 nmol胃促生长素可显著刺激雄性犊牛生长激素的释放（P<0.05）。这些结果表明，胃饥饿素是反刍动物一种有效的生理性生长激素分泌剂。少

Ghrelin, a novel endogenous growth hormone (GH) secretagogue, has been shown to exert very potent and specific GH-releasing activity in rats and humans. However, little is known about its GH-releasing activity and endocrine effects in domestic animals. To clarify the effects of ghrelin on GH secretion in ruminants, GH-releasing effects of ghrelin were examined in vitro and in vivo in goats and cattle. GH-releasing effects of human ghrelin (hGhrelin) and rat ghrelin (rGhrelin) on bovine anterior pituitary (AP) cells were compared with those of GH-releasing hormone (GHRH) in vitro. hGhrelin and rGhrelin significantly stimulated GH release from the cultured cells at doses from 10^<-10> to 10^<-7> M and from 10^<-9> to 10^<-7> M, respectively (P<0.05). However, GH-releasing effects of ghrelin were weaker than that of GHRH. When hGhrelin (10^<-8>M) and GHRH (10^<-8>M) were added together, the release of GH induced by both peptides was significantly greater than that by hGhrelin alone (P<0.0 … More 5), and tended to be greater than that by GHRH alone. Somatostatin (SS, 10^<-7> M) significantly blunted GH release induced by hGhrelin (10^<-8>M) and GHRH (10^<-8>M) (P<0.05). In the presence of SS, additive effects of hGhrelin and GHRH on the release of GH were observed (P<0.05). These in vitro results in cattle were similar to those in pigs. To clarify the effect of ghrelin on GH secretion in vivo in ruminants, plasma GH responses to intra-arterial and intra-hypothalamic injections of rGhrelin were examined in goats and cattle. The infra-arterial injection of 3 μg/kg BW of rGhrelin in ovariectomized goats significantly increased plasma GH concentrations (P<0.05). However, the secretory response to 3 μg/kg BW of rGhrelin was weaker than that of GHRH (0.25μg/kg BW). An infusion of 10 nmol of ghrelin into the medial basal hypothalamus (arcuate nucleus) significantly stimulated the release of GH in male calves (P<0.05). These results show that ghrelin is one of potent physiological GH secretagogues in ruminants. Less