Peptide Therapy Foundations: Secretagogues
Course Details
This course examines the growth hormone secretagogues as a working class: the peptides and small molecules that prompt the pituitary to release growth hormone rather than supplying the hormone directly. It is built for clinicians who want to understand how each agent acts, where the evidence sits, and how the choices differ at the level of receptor, half-life, and signaling pattern.
The lessons fall into two broad families. The first is the GHRH analogs, including Sermorelin, Mod GRF 1-29, CJC-1295, and Tesamorelin, which engage the growth hormone releasing hormone receptor and tend to preserve the body’s pulsatile, feedback-controlled secretion. The second is the ghrelin and growth hormone secretagogue receptor agonists, including Ipamorelin, Hexarelin, GHRP-2, GHRP-6, MK-677, and Anamorelin, which act through a separate pathway and vary in selectivity, potency, and off-target signaling.
Each lesson is grounded in the same clinical lens: what the agent is, how it works, what the evidence shows, and what a practitioner weighs before applying it. Together they give you a comparative map of the class so you can reason about an individual peptide in the context of its alternatives.
SSRP FACULTY
William Seeds, MD
William Seeds, MD
William Seeds, MD
Before establishing the SSRP Institute, Dr. Seeds served as a board-certified orthopedic surgeon and sports medicine specialist for nearly three decades, including Chief of Surgery, Orthopedic Residency Site Director, and Director of The Ohio Bone & Joint Institute for University Hospitals.
His significant contributions to sports medicine have been recognized at the NFL Hall of Fame. He has consulted for athletes across all major sports leagues, including the NFL, NHL, MLB, NBA, and even the performers on “Dancing with the Stars.”
Through his research at the SSRP Institute, Dr. Seeds continues to explore the cellular pathways and mechanisms that positively impact disease and dysfunction in the body as well as optimize physical performance.
GHRP-6
In-ProgressLesson Resources
Overview
GHRP-6 is a synthetic hexapeptide growth hormone secretagogue, derived from a met-enkephalin analog and first described by Cyril Bowers in the 1980s. What distinguishes it from other GHRPs is a dual receptor system. It acts as a super-agonist at the growth hormone secretagogue receptor 1A, the ghrelin receptor, and it engages the CD36 receptor more meaningfully than GHRP-2 does. That second pathway is where much of its broader tissue activity originates.
At the pituitary, GHSR-1A activation drives the PLC, IP3, DAG, and PKC cascade, raising intracellular calcium and triggering growth hormone release through vesicular exocytosis. GHRP-6 also suppresses somatostatin, giving it a dual mechanism that amplifies a pulsatile, physiologic growth hormone pulse rather than a continuous signal. The CD36 pathway, working through PPAR-gamma, down-regulates TGF-beta 1 and connective tissue growth factor, which the transcript links to anti-fibrotic and cytoprotective effects across cardiac, hepatic, and other tissue.
On administration, subcutaneous dosing in the transcript centers on roughly 100 to 300 micrograms per injection, with 100 micrograms cited as a sensible general reference. Carbohydrates and fats can blunt the growth hormone response, so timing favors a fasted state, first thing in the morning and again at night, avoiding carbs and fats for about 30 minutes after and 90 minutes to two hours before injection. Pure protein such as whey is described as acceptable. Dosing can run one to three times daily to support physiologic pulses.
The transcript also describes synergy when GHRP-6 is paired with a GHRH such as sermorelin, tesamorelin, or CJC-1295. The two converge on growth hormone exocytosis through independent cascades, an effect that depends on an intact hypothalamic-pituitary axis. Combining two GHRPs is not advised.
For monitoring, the lesson points to serial IGF-1 levels, a growth hormone response check 15 to 30 minutes post-injection, and quarterly InBody or DEXA tracking of lean and fat mass. Watch for water retention and appetite changes.
Key clinical points
- Pulsatile, not suppressive: Because release stays pulsatile, the peptide preserves pituitary feedback loops and carries a lower risk of growth hormone receptor desensitization than continuous exogenous growth hormone.
- Cytoprotective signaling: Preclinical and largely rat-model evidence describes preserved mitochondrial integrity, reduced fibrosis and infarct scarring, and a shift in BCL-2 to apoptotic protein ratios that favors cell survival.
- Strongest appetite effect: As the most ghrelin-mimetic of the GHRPs, GHRP-6 stimulates appetite more than GHRP-2, ipamorelin, or hexarelin, a consideration when food intake is a treatment goal.
- Transient hormonal shifts: Expect self-limiting cortisol and prolactin elevation, which runs higher with GHRP-6 than with GHRP-2 or ipamorelin.
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