The stability problem
GHRH is cleaved rapidly by DPP-4 near its N-terminus. Analogues address this by modifying or protecting the cleavage site — tesamorelin, for example, carries an N-terminal modification that blocks that route.
What acting upstream preserves
Because a GHRH analogue stimulates the pituitary rather than replacing growth hormone, release remains pulsatile and feedback continues to operate. The system retains its regulation, which is the principal difference from supplying growth hormone directly.
What research examines
GHRH receptor binding and signalling, the growth hormone and IGF-1 response downstream, and metabolic endpoints in clinical study populations. Comparisons between analogues concern stability and receptor selectivity rather than a different mechanism.
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