Ghrelin Receptors Discovered in Human Hypothalamus and Pituitary Gland

Ghrelin, often called the 'hunger hormone', is a peptide primarily produced in the stomach that plays a crucial role in regulating appetite, energy balance, and stimulating growth hormone (GH) release. While its primary receptor, the growth hormone secretagogue receptor (GHSR-1a), was known, its precise distribution and binding characteristics in key human brain regions like the hypothalamus (a control center for many bodily functions) and the pituitary gland (which produces GH) were not fully established. This study aimed to confirm and characterize specific ghrelin receptor binding sites in membranes from human hypothalamus and pituitary gland tissues.

The study successfully identified specific, high-affinity, and saturable binding sites for 125I-labeled ghrelin in both human hypothalamic and pituitary membranes. In the hypothalamus, a robust binding site was characterized with a dissociation constant (Kd) of approximately 0.2-0.5 nM (nanomolar), indicating very strong binding affinity, and a maximal binding capacity (Bmax) of 50-80 fmol/mg protein (femtomoles per milligram of protein), signifying a substantial number of receptors. Similarly, pituitary membranes exhibited specific ghrelin binding with a Kd in the range of 0.3-0.6 nM and a Bmax of 30-60 fmol/mg protein, confirming direct receptor presence in this gland. The binding was shown to be highly specific, as unlabeled ghrelin effectively displaced 125I-labeled ghrelin with an IC50 (concentration causing 50% inhibition of binding) of approximately 1-2 nM, demonstrating a selective interaction with the ghrelin receptor. Other structurally unrelated peptides showed negligible displacement, further validating the specificity of the observed binding.