Growth hormone secretagogue (revision 8)
Old revision·12:07, 2 Feb 2025·UnderfillUna
| Growth hormone secretagogueResearch peptides | |
|---|---|
| Two receptor families | GHRH receptor; ghrelin receptor (GHS-R1a) |
| GHRH analogues | Sermorelin, CJC-1295, Tesamorelin |
| Ghrelin-receptor agonists | Ipamorelin, and related compounds |
| Approved example | Tesamorelin, for a specific indication |
| Topic infobox · conventions | |
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]
Mechanisms
[edit]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]
Evidence and status
[edit]Tesamorelin is approved for a specific indication — reduction of excess visceral adipose tissue in a defined population — and has trial evidence supporting it. Most other compounds in this group are not approved for any indication and are distributed as research chemicals.[2]
The evidence base for the unapproved compounds is thin: small studies, short durations, surrogate endpoints such as growth hormone or IGF-1 concentration rather than clinical outcomes, and in several cases no controlled human data at all.[1]
References
- ^ a b c d e f Sigalos JT, Pastuszak AW. "The safety and efficacy of growth hormone secretagogues." Sexual Medicine Reviews 6(1):45–53 (2018). PMID 28526632.
- ^ a b Molitch ME, Clemmons DR, Malozowski S, et al. "Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline." Journal of Clinical Endocrinology and Metabolism 96(6):1587–1609 (2011). PMID 21602453.