Arvat E, Camanni F, Ghigo E
Department of Internal Medicine, University of Turin, Italy.
Acta Paediatr Suppl. 1997 Nov;423:92-6. doi: 10.1111/j.1651-2227.1997.tb18383.x.
Growth hormone-releasing peptides (GHRPs) are synthetic molecules with strong, dose-related and reproducible growth hormone (GH)-releasing activity in humans. GHRPs act at both the pituitary and the hypothalamic level, where specific receptors have been located. In adults, GHRPs release more GH than does GH-releasing hormone (GHRP), whilst their co-administration has a synergistic effect, indicating that they have, at least partially, different mechanisms of action. However, normal activity of GHRH-secreting neurones is needed to achieve the full GH-releasing effect of GHRPs. In contrast to GHRH, the GH-releasing activity of GHRPs is not further increased by substances acting via inhibition of hypothalamic somatostatin, and is only blunted by substances that stimulate hypothalamic somatostatin release. Even free fatty acids and exogenous somatostatin, which act directly on somatotrophs, do no more than blunt the effect of GHRPs. Thus, the GH-releasing activity of GHRPs is partially refractory to inhibitory influences, GHRPs act, at least in part, by antagonism of somatostatin activity, both at the pituitary and the hypothalamic level. The GH-releasing effect of GHRPs is not dependent on gender, but undergoes age-related variations. Gonadal steroids seem to influence the activity of GHRPs only in childhood. The reduced GH response to GHRPs in the elderly is probably due mainly to concomitant GHRH hypoactivity and somatostatinergic hyperactivity. A preserved GH-releasing effect of GHRPs has been reported in acromegaly, anorexia nervosa, hyperthyroidism and in critically ill patients. GHRPs have also been found to increase GH release in children with idiopathic short stature, in GH deficiency and in obese patients, in whom there is a well-known reduction of somatotroph function. The GH response to GHRPs is markedly reduced in hypothyroidism and Cushing's syndrome.
生长激素释放肽（GHRPs）是一类合成分子，在人体内具有强大的、剂量相关且可重复的生长激素（GH）释放活性。GHRPs作用于垂体和下丘脑水平，在这些部位已定位到特定受体。在成年人中，GHRPs比生长激素释放激素（GHRH）释放更多的GH，而它们联合使用具有协同作用，这表明它们至少部分具有不同的作用机制。然而，需要GHRH分泌神经元的正常活动才能实现GHRPs的完全GH释放效应。与GHRH相反，通过抑制下丘脑生长抑素起作用的物质不会进一步增加GHRPs的GH释放活性，而仅被刺激下丘脑生长抑素释放的物质减弱。即使是直接作用于生长激素细胞的游离脂肪酸和外源性生长抑素，也只不过是减弱GHRPs的作用。因此，GHRPs的GH释放活性对抑制性影响部分具有抗性，GHRPs至少部分地通过拮抗垂体和下丘脑水平的生长抑素活性来发挥作用。GHRPs的GH释放效应不依赖于性别，但会随年龄变化。性腺类固醇似乎仅在儿童期影响GHRPs的活性。老年人对GHRPs的GH反应降低可能主要是由于伴随的GHRH活性低下和生长抑素能活性亢进。据报道，在肢端肥大症、神经性厌食症、甲状腺功能亢进症和重症患者中，GHRPs的GH释放效应得以保留。在特发性身材矮小儿童、生长激素缺乏症儿童和肥胖患者中也发现GHRPs可增加GH释放，在这些患者中生长激素细胞功能有众所周知的降低。甲状腺功能减退症和库欣综合征患者对GHRPs的GH反应明显降低。
