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In combination research protocols, published models have explored GHRH analogues paired with ipamorelin exploiting a synergistic mechanism whereby GHRH receptor activation and GHS-R1a activation cooperate to amplify GH pulse amplitude beyond either compound alone

Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA)

further supports this idea by highlighting preliminary findings wherein GHRH analogs and GHS-R agonists applied separately appeared to elevate pulsatile GH secretion, with reports indicating approximately 20-fold and 47-fold increases above baseline

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