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Ipamorelin’s selectivity for GH release over cortisol, ACTH, and prolactin co-stimulation is conferred primarily by its Aib³ (α-aminoisobutyric acid) substitution — a non-natural alpha-methyl amino acid that constrains the peptide backbone conformation in a manner that optimises GHS-R1a engagement at somatotrophs while reducing interactions with GHS-R1a expressing hypothalamic CRH neurons responsible for ACTH/cortisol co-stimulation