Growth hormone secretagogues in pathological states: diagnostic implications

Abstract

Golubicic I, Nikitovic M, Mitrovic N, Dieguez C, Casanueva FF. Growth hormone secretagogues in pathological states: diagnostic implications. Acta Paediatr 1997; Suppl423:97-101. Stockholm.The identification and cloning of the receptor for synthetic growth hormone (GH) secretagogues, even before the endogenous ligand has been identified or its precise physiological role established, suggests that there is a novel target of action for this class of drug. In an attempt to select patients who will benefit from GH treatment, GH secretagogues are being evaluated for their usefulness in diagnosing GH deficiency. The effects of GH-releasing peptides (GHRPs) on GH release as a function of age and metabolic status, and in different neuroendocrine pathologies, are described, as are the different mechanisms of action, potency and reproducibility of the response to GHRPs compared with GH-releasing hormone (GHRH). GHRPs offer the advantage over GHRH in natural models of deranged GH secretion in that, in various metabolic states (e.g. obesity, anorexia nervosa and non-insulin-dependent diabetes mellitus), the GH response to GHRH is more impaired than it is to GHRPs. However, in some neuroendocrine pathologies, the reverse is true. Thus, both secretagogues provide separate information on the physiological status of somatotrophs. Growth hormone-releasing peptide-6, growth hormone-releasing hormone, hexarelin, metabolic derangements, neuroendocrine pathologies V Popovic, Institute of Endocrinology, University Clinical Centre, Belgrade, Yugoslavia ISSN 0803-5326Neuroendocrine control of the pulsatile pattern of growth hormone (GH) secretion is complex. The multicomponent nature of the neuronal network and the complex transcriptional machinery that regulates GH gene expression have been characterized (1). In addition to the specific hypothalamic regulatory' hormones -GHreleasing hormone (GHRH) and somatdstatinother substances can influence GH secretion, namely pituitary cyclic AMP, oestrogens, glucocorticoids, GH-releasing peptides (GHRPs) and their nonpeptide pharmacological analogues. Metabolic states, such as obesity and malnutrition, and even metabolites, such as glucose, amino acids and free fatty acids, also participate in the control of GH secretion (2-4).In an attempt to improve our understanding of the complicated regulation of GH secretion in humans, and its relevance to clinical practice, we have studied the effects of GHW-6 and hexarelin, which is an analogue of GHRP-6 containing a 2-methyl substitution of D-tryptophan. Such small synthetic hexapeptides have no sequence homology with GHRH and are characterized by their high potency and selectivity in the reIease of GH in different clinical conditions (metabolic and neuroendocrine) associated with altered or impaired GH secretion. The well-known GHRP-6 (5, 6) acts through a specific receptor. This has recently been cloned and supports the existence of a second route of GH regulation, although the endogenous ligand for this receptor has not yet been identified. The GHRP-6 ...

Hexarelin as a test of pituitary reserve in patients with pituitary disease

“…It has been suggested that the combination of GHRH and GH secretagogues, the strongest GH‐releasing test known ( Ghigo et al ., 1997 ), might be useful in the diagnosis of adult GHD. Popovic et al . (1997 ) found no overlap between hypopituitary patients and healthy young or elderly control subjects in the GH response to GHRH + GHRP‐6, and suggested that this test could be useful in the diagnosis of adult GHD.…”

Effects of Eight Months Treatment with Graded Doses of a Growth Hormone (GH)-Releasing Peptide in GH-Deficient Children1

“…G ROWTH hormone (GH) deficiency can arise from a variety of causes, but many patients with idiopathic isolated GH deficiency (GHD) have a deficiency of hypothalamic GH-releasing hormone (GHRH) or interruption of the flow of GHRH to the pituitary (1,2), rather than an instrinsic pituitary defect, and are capable of responding to administered synthetic GHRH with a rise in GH (3,4). The response may initially be low or undetectable due to chronic GHRH deficiency and somatotroph atrophy, but it usually rises after repeated GHRH stimulation (5).…”