Ghrelin is orexigenic hormone primarily synthesized by endocrine X/A-like cells of gastric
oxyntic mucosa to stimulate appetite and food intake along with regulation of growth hormone and insulin
secretion; glucose and lipid metabolism; gastrointestinal motility; blood pressure, heart rate and
neurogenesis. Furthermore, peripherally (after crossing the blood brain barrier) as well as centrally
synthesized ghrelin (in the hypothalamus) regulates diverse functions of central nervous system including
stress-associated behavioral functions. Exposure to stress alters the ghrelin levels and alteration in
ghrelin levels significantly affects neuro-endocrinological parameters; metabolism-related physiology,
behavior and mood. Studies have shown both anxiolytic and anxiogenic role of ghrelin suggesting its
dual role in modulating anxiety-related behavior. However, it is proposed that increase in ghrelin levels during stress condition
is an endogenous stress coping behavior and increased ghrelin levels may be required to prevent excessive anxiety.
In preclinical and clinical studies, an elevation in ghrelin levels during depression has been correlated with their antidepressant
activities. Ghrelin-induced modulation of stress and associated conditions has been linked to alteration in hypothalamic-
pituitary-adrenal (HPA) axis; autonomic nervous system (mainly sympathetic nervous system and serotonergic
neurotransmission. A reciprocal relationship has been reported between corticotropin-releasing hormone (CRH) and ghrelin
as ghrelin increases the release of CRH, ACTH and corticosteroids; while CRH decreases the expression of ghrelin.
Similarly, ghrelin increases the serotonin turnover and in turn, serotonin controls ghrelin signaling to modulate anxietyrelated
behavior. The present review discusses the dual role of ghrelin in stress and related behavioral disorders along with
Keywords: Ghrelin, serotonin, stress, anxiety, depression, corticosteroids.
Rights & PermissionsPrintExport