{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The growth hormone secretagogue receptor (GHSR) is a multifunctional G‐protein–coupled receptor whose actions extend well beyond the well‐documented regulation of growth hormone secretion and food intake. In the central nervous system, GHSR is highly expressed in key hypothalamic neurons such as those co‐expressing neuropeptide Y and agouti‐related protein, where it regulates mitochondrial function, neuronal activation, and synaptic plasticity to promote orexigenic behavior and growth hormone pulsatility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In peripheral tissues, activation of GHSR by ghrelin has been shown to couple metabolic signals with endocrine responses by regulating insulin, glucagon, and lipogenic pathways in hepatocytes and adipocytes. Such actions not only drive pancreatic hormone release and adipocyte proliferation but also promote lipogenesis, thereby coordinating nutrient availability with energy storage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": " Furthermore, GHSR exhibits unusually high ligand‐independent (constitutive) activity that is critical for normal physiological processes; mutations that selectively impair this basal signaling have been linked to growth failure and metabolic dysregulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": " GHSR signaling is further modulated by its ability to form heterodimers with other receptors—including dopamine 1, melanocortin 3, and 5-HT2C receptors—which can finely tune downstream effector pathways involved in appetite regulation and reward processing."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "20"}]}, {"type": "t", "text": " In addition to its metabolic and neuroendocrine roles, GHSR activation in immune cells dampens proinflammatory cytokine production and thereby contributes to the regulation of inflammatory processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " Finally, endogenous modulators such as liver‐expressed antimicrobial peptide 2 (LEAP2) interact with GHSR to antagonize ghrelin’s actions and refine receptor signaling in accordance with the nutritional state."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": " Collectively, these findings demonstrate that GHSR functions as a central integrator of endocrine, metabolic, and immunological signals. Its diverse roles in both the central nervous system and peripheral tissues highlight its promise as a therapeutic target for metabolic diseases, growth disorders, and inflammatory conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vishwa Deep Dixit, Eric M Schaffer, Robert S Pyle, et al. 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