8 Growth hormone releasing hormone

Human growth hormone releasing hormone (GHRH) was originally extracted from two pancreatic tumours in patients with acromegaly, and is now known to consist of a 44 residue amidated peptide or its C-terminal-shortened derivatives. The sequence of rat GHRH has also been determined; this 43 residue peptide shows approximately 70% homology with human GHRH, and is located mainly in the arcuate nucleus of the hypothalamus. Pulsatile GH release in the rat is principally a consequence of the pulsatile release of hypothalamic GHRH, although this appears to be associated with a transient suppression of somatostatin release. Exogenous GHRH specifically increases circulating GH in many species, and in the long term may increase growth.

In normal man, several analogues of GHRH have been shown to be safe, sensitive and specific stimuli to GH release; although there may be a variable prolactin response, this is usually of small magnitude. Continuous infusion of GHRH leads to a decrement in responsiveness, due at least in part to changes in hypothalamic somatostatin. The GH response to GHRH is also modulated by obesity, blood sugar, free fatty acids, and GH itself. Many children with ‘GH deficiency’ (idiopathic, radiation-induced, or secondary to hypothalamopituitary tumours) respond to intravenous GHRH with an acute rise in serum GH.

Early studies also indicate that long-term therapy with subcutaneous GHRH may increase growth velocity in some of these children. It is concluded that analogues of GHRH are useful in the investigation of the hypothalamopituitary axis, and may be important in the therapy of short stature.