Growth hormone-releasing hormone. The physiopathologic aspects and its diagnostic-therapeutic use]

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.