Growth hormone secretagogue (revision 5)

Growth hormone secretagogues are compounds that stimulate release of endogenous growth hormone, in contrast to administration of growth hormone itself. Two receptor families are involved: the receptor for growth hormone-releasing hormone, and the ghrelin receptor GHS-R1a.^[1]

GHRH analogues — sermorelin, CJC-1295, tesamorelin — mimic the hypothalamic releasing hormone. Ghrelin-receptor agonists such as ipamorelin act at a separate receptor and by a partly complementary mechanism.^[1]

Because they act through the pituitary rather than replacing the hormone, the resulting secretion retains its pulsatile pattern and remains subject to negative feedback — which limits the achievable exposure and is the main pharmacological argument for the approach.^[1]

GHRH-receptor agonism at somatotroph cells raises cAMP and promotes synthesis and release of growth hormone. Native GHRH has a very short half-life; the analogues are modified to extend it, and CJC-1295 uses a linker permitting covalent binding to albumin for a much longer duration.^[1]

Ghrelin-receptor agonism acts through a different pathway and also suppresses somatostatin tone, so the two mechanisms combine more than additively in some experimental settings — the rationale for combining them that appears in community discussion.^[1]

Feedback remains intact in both cases: rising growth hormone and insulin-like growth factor 1 suppress further release. This is the mechanistic reason a secretagogue cannot produce the exposures achievable with exogenous growth hormone.^[2]