De Marinis L, Mancini A, La Brocca A, D'Amico C, Sambo P, Tofani A, Barbarino A
Università Cattolica del Sacro Cuore, Roma, Istituto di Endocrinologia.
Minerva Med. 1989 Apr;80(4):325-34.
The object of the present study is to review all that in the last years has been discovered about growth hormone-releasing hormone (GHRH), in order to point out both its physiopathological characteristics and its possible diagnostic and therapeutic use. In the first section are summarily reviewed the different studies that culminated in 1982 with the identification of three GRF: GRF(1-37)-OH, GRF(1-40)-OH and GRF(1-44)-NH2, the last of which, by immunohistochemical methods, resulted to be similar to the hypothalamic hGHRH. Then we describe the anatomic distribution of GHRH in man, and its mechanism of action at both receptor and postreceptor levels. On the other hand, the control of the GHRH secretion by peptidergic hypothalamic neurons occurs through four principal monoaminergic systems such as dopaminergic, noradrenergic, adrenergic and serotoninergic ones, and also by cholinergic fibers and by endogenous opiates, all acting to cause the release, into the hypothalamo-hypophyseal portal circulation, of GHRH. In the second section is attracted attention on the GHRH as a diagnostic agent in the two diseases that represent the main alterations of the GH secretion: acromegaly and short stature. According to the different studies considered, it may be concluded that GHRH testing has limited diagnostic usefulness in the clinical evaluation of acromegaly, but allows to discriminate acromegalic patients with ectopic production of GHRH from those with pituitary tumors. For what concerns short stature, the results of observation realized both in adult subjects and in children, all with GH deficiency, by exogenous administration of GHRH, have pointed out that the majority of the GH deficiency patients have hypothalamic disregulation, and not a pure pituitary deficiency as it has been supposed before GHRH discovery. In the third section is attracted attention on the GHRH as a therapeutic agent. Its possible use in the therapy of the children with GH deficiency is of considerable interest, above all in relation to the hypothalamic pathogenesis of their short stature.
本研究的目的是回顾过去几年中有关生长激素释放激素（GHRH）的所有发现，以指出其生理病理特征及其可能的诊断和治疗用途。在第一部分中，简要回顾了不同的研究，这些研究在1982年最终确定了三种生长激素释放因子：GRF(1 - 37)-OH、GRF(1 - 40)-OH和GRF(1 - 44)-NH2，其中最后一种通过免疫组化方法显示与下丘脑的人GHRH相似。然后我们描述了GHRH在人体中的解剖分布，以及它在受体和受体后水平的作用机制。另一方面，肽能下丘脑神经元对GHRH分泌的控制通过四个主要的单胺能系统，如多巴胺能、去甲肾上腺素能、肾上腺素能和5-羟色胺能系统，以及胆碱能纤维和内源性阿片肽来实现，所有这些都作用于促使GHRH释放到下丘脑-垂体门脉循环中。在第二部分中，关注了GHRH作为诊断剂在两种代表生长激素分泌主要改变的疾病中的应用：肢端肥大症和身材矮小。根据所考虑的不同研究，可以得出结论，GHRH检测在肢端肥大症的临床评估中诊断价值有限，但可以区分异位产生GHRH的肢端肥大症患者和垂体肿瘤患者。对于身材矮小，通过对所有生长激素缺乏的成人和儿童进行外源性GHRH给药的观察结果表明，大多数生长激素缺乏患者存在下丘脑调节异常，而不是如在GHRH发现之前所认为的单纯垂体缺乏。在第三部分中，关注了GHRH作为治疗剂的应用。它在治疗生长激素缺乏儿童中的可能用途具有相当大的意义，尤其是考虑到他们身材矮小的下丘脑发病机制。
