Growth hormone secretagogue

Growth hormone secretagogues (GHS) are compounds — peptide or small-molecule — that stimulate the pituitary to release endogenous growth hormone (GH). They act through one of two receptors: the ghrelin/GHS receptor (GHSR-1a) or the GHRH receptor.

Mechanisms

• GHSR-1a agonists mimic ghrelin and produce a sharp, short-lived GH pulse. Examples include the peptide ipamorelin and the orally bioavailable small molecule ibutamoren (MK-677).
• GHRH receptor agonists mimic endogenous growth-hormone-releasing hormone and produce a more physiological, sustained release. Examples include sermorelin and the long-acting analogue CJC-1295.

The two classes are commonly stacked because their effects on GH release are additive: a GHRH agonist raises the baseline secretory tone, and a ghrelin-receptor agonist superimposes a pulse on top.

Distinction from exogenous GH

A GHS raises endogenous GH and, downstream, hepatic IGF-1. Unlike injected recombinant GH, the effect is gated by the body’s negative-feedback loops (somatostatin in particular), so achievable peaks are lower and side effects related to chronic supraphysiological GH are typically milder. The downstream hormonal effects — and the WADA classification — are nonetheless the same.

Status

GHS are prohibited in and out of competition under WADA section S2 and banned by all major natural-bodybuilding federations.