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Mechanism Comparison Shared Pathway Both peptides activate GHSR-1a on pituitary somatotrophs, triggering: GHSR-1a Gq/11 PLC IP + DAG intracellular Ca release PKC activation Ca influx GH vesicle exocytosis This is fundamentally different from how GHRH analogs (CJC-1295, Sermorelin) work (GHRHR Gs cAMP PKA), which is why combining either GHRP with a GHRH analog produces synergistic GH release (Veldhuis et al., 2009)

This secretion then stimulates Leydig cells to generate testosterone and Sertoli cells to facilitate sperm development

doi: 10.2217/bmm-2020-0308 7 QiXMWangJXuXXLiYYWuYG

However, inhibitors can affect more than one target, so genetic tests and direct binding studies provide stronger support

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doi: 10.1038/s41467-020-18336-5 132 TaglialegnaA.NavarroS.VenturaS.GarnettJ