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-2
In-ProgressLesson Resources
Overview
GHRP-2 is a hexapeptide growth hormone secretagogue and the most potent of the GHRP class. It binds the GHS-R1A ghrelin receptor, the common receptor shared across the GHRPs, and acts at both the pituitary and the hypothalamus. Approved in Japan as a diagnostic agent (KP-102), it remains investigational in the US and is classified by WADA as a banned S2 peptide hormone.
How it works
GHRP-2 stimulates pulsatile growth hormone secretion, the physiologic rhythm clinicians look to support. It works through two complementary actions: direct activation of the GHS-R1A receptor on the anterior pituitary, and attenuation of somatostatin tone, the inhibitory control that rises with age and disease. By reducing somatostatin and promoting hypothalamic growth hormone releasing hormone, it adds a third layer that upregulates growth hormone production. It does not require an intact GHRH receptor to act.
Downstream, GHRP-2 engages several intracellular pathways: PLC/IP3/DAG signaling tied to calcium influx and growth hormone exocytosis, cyclic AMP/PKA driving gene transcription, protein kinase C, and CREB activation supporting growth hormone synthesis. Separately, through CD36 scavenger receptor binding and the PI3K/AKT survival pathway, it shows cytoprotective and anti-inflammatory properties in preclinical cardiac and neuronal studies. These pleiotropic pathways reflect the recurring theme of cell efficiency, flexibility, and responsiveness.
Dosing considerations
Research-based titration starts near 100 micrograms subcutaneously once daily, often in the evening to align with the nocturnal growth hormone rhythm. Staying at 100 micrograms helps avoid desensitization and enables multiple daily dosing. Monitoring can include growth hormone, IGF-1 response, fasting glucose, and tolerance. GHRP-2 also shows synergistic release when paired with a GHRH peptide such as CJC-1295 or tesamorelin.
Key clinical points
- Potency: Highest growth hormone release of the compared GHRPs, above GHRP-6 and ipamorelin, with a half-life around twenty to thirty minutes.
- Age-independent response: Studies show elderly patients respond similarly to young adults, and obese individuals retain responsiveness.
- Appetite: A ghrelin mimetic with moderate orexigenic effects, less intense than GHRP-6, with a potential role in cachexia and anorexia.
- Cortisol: Mild ACTH and cortisol release, useful diagnostically for secondary adrenal evaluation and gentler than GHRP-6.
- Desensitization: Higher doses drive receptor desensitization. In healthy males, peak release nearly halved by day five at 100 micrograms, then leveled off.
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