A Ghrelin Agonist is a compound, either endogenous or pharmaceutical, that binds to and activates the Ghrelin Receptor (GHSR-1a), mimicking the action of the native hormone ghrelin. This activation primarily targets the hypothalamus and pituitary gland, resulting in a potent orexigenic effect, which stimulates appetite and food intake. Beyond its role in energy balance, a ghrelin agonist also typically stimulates the release of Growth Hormone (GH) from the anterior pituitary. Clinical interest focuses on its potential therapeutic application in conditions involving cachexia or growth hormone deficiency.
Origin
The term is derived from the hormone “Ghrelin,” which was discovered in 1999, and the pharmacological suffix “agonist,” from the Greek agonistes meaning competitor or combatant, signifying a substance that initiates a physiological response. Ghrelin itself is an acronym for Growth Hormone-Releasing Peptide, emphasizing its dual role in appetite and somatotropic function. The term thus belongs to the domain of peptide endocrinology and receptor pharmacology.
Mechanism
The agonist binds to the GHSR-1a receptor, a G protein-coupled receptor, predominantly expressed in the arcuate nucleus of the hypothalamus and the pituitary. This binding activates intracellular signaling pathways, such as the phospholipase C pathway, leading to the stimulation of neuropeptide Y (NPY) and agouti-related protein (AgRP) neurons in the hypothalamus, which drives the sensation of hunger. Concurrently, in the pituitary, this action potentiates the release of growth hormone, influencing systemic metabolism and anabolism.
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