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

Ghrelin是一种新的内源性生长激素(GH)促分泌剂，已被证明在大鼠和人类身上具有非常强大和特异的GH释放活性。然而，对其在家畜体内的生长激素释放活性和内分泌作用知之甚少。为了阐明Ghrelin对反刍动物GH分泌的影响，在山羊和牛体内检测了Ghrelin对GH的释放效果。比较人Ghrelin(HGhrelin)和大鼠Ghrelin(RGhrelin)体外对牛垂体前叶(AP)细胞的GH释放作用，并与GH释放激素(GHRH)进行比较。HGhrelin和rGhrelin分别在10^~10和10^~7、10^~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、10~10、但Ghrelin的GH释放作用弱于GHRH。当hGhrelin(10^~(-8)M)和GHRH(10^；~(-8)M)共同作用时，两种多肽诱导的GH释放均显著大于hGhrelin单独作用(P&lt；0.0…5)较多，且有大于GHRH单独作用的趋势。生长抑素显著抑制hGhrelin和GHRH诱导的GH释放(P&lt；0.05)。在SS存在的情况下，hGhrelin和GHRH对GH的释放有相加作用(P&lt；0.05)。在牛身上的这些体外结果与在猪身上的结果相似。为了阐明Ghrelin对反刍动物体内GH分泌的影响，研究了动脉注射和下丘脑注射Ghrelin对山羊和牛血浆GH的影响。去卵巢山羊动脉注射3μg/kg体重的重组Ghrelin后，血浆GH浓度显著升高(P&lt；0.05)。RGhrelin对3μg/kgbw的分泌反应弱于Ghrh(0.25μg/kgbw)。向下丘脑内侧基底核(弓状核)注入10nmolGhrelin可显著刺激雄性小牛GH的释放(P&lt；0.05)。这些结果表明，Ghrelin在反刍动物体内是一种有效的生理性生长激素促分泌剂。较少

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