Growth Hormone Secretagogue Binding Sites in Peripheral Human Tissues1

The family of GH secretagogues (GHS) includes peptidyl (hexarelin) and nonpeptidyl (MK 0677) molecules possessing specific receptors in the brain, pituitary, and thyroid. GHS receptor subtypes have also been identified in the heart; and a gastric-derived peptide, named ghrelin, has recently been proposed as a natural ligand. Our aim was to investigate the presence of GHS receptors in a wide range of human tissues, by radioreceptor assay with[ 125I]Tyr-Ala-hexarelin. GHS receptors were detected mainly in the myocardium, but they were also present (in order of decreasing binding activity) in adrenal, gonads, arteries, lung, liver, skeletal muscle, kidney, pituitary, thyroid, adipose tissue, veins, uterus, skin, and lymphnode. In contrast, negligible binding was found in parathyroid, pancreas, placenta, mammary gland, prostate, salivary gland, stomach, colon, and spleen. Hexarelin, MK 0677, and human ghrelin completely displaced the radioligand from binding sites of endocrine tissues, but MK 0677 and ghrelin were less potent than hexarelin. In nonendocrine tissues, both MK 0677 and ghrelin were inactive in displacement of [125I]Tyr-Ala-hexarelin, whereas hexarelin was as active as a displacing agent in endocrine tissues. This study provides the first detailed analysis of the tissue localization of GHS receptors and suggests that a still unknown receptor subtype, specific for peptidyl GHS, may exist in the heart and in other tissues.