This review maps the full spectrum of GH-releasing substances from GHRP-6 to MK-677, their receptor types, and how the discovery of the natural ligand ghrelin transformed the field.
Drugs predicted a hormoneSynthetic GH secretagogues led to GHS-R cloning, which predicted ghrelin's existence before its discovery — reverse pharmacology in action
What the researchers found
Structurally diverse GH secretagogues (peptides and non-peptides) all converge on the GHS receptor, whose cloning predicted the existence of a natural ligand — later identified as ghrelin — with widespread physiological roles beyond GH release.
Why it matters
This review captures a pivotal moment when synthetic GH secretagogues led to the discovery of a major new hormone (ghrelin), demonstrating how drug development can reveal fundamental biology.
How the study worked
Comprehensive review of GH-releasing substance pharmacology, receptor biology, and physiological significance, covering peptide and non-peptide secretagogues.
What this study cannot tell us
Review from 1999, just before ghrelin's formal identification. Some receptor characterization was preliminary.
How to read the evidence
Strong evidence from a comprehensive review synthesizing pharmacological, molecular, and physiological data from the entire GH secretagogue field.
When this study was published
Published in 1999, just before ghrelin's identification in 1999. This review captures the state of knowledge at this historic transition.
The bigger picture
The GH secretagogue story is a remarkable example of reverse pharmacology — synthetic drugs were developed before the natural hormone (ghrelin) was discovered. This revolutionized understanding of appetite, metabolism, and GH regulation.
Questions still open
- What is the natural function of the GHS-R system?
- Can receptor subtype-selective drugs target specific tissues?
- How does the ghrelin system interact with other metabolic hormones?
Common questions
What's the connection between GH peptides and the hunger hormone?
Why are there so many different GH secretagogues?
Read the original research
Growth hormone releasing substances: types and their receptors.
Hormone research, 51 Suppl 3, 1-8
Citation
Smith, R G; Palyha, O C; Feighner, S D; Tan, C P; McKee, K K; Hreniuk, D L; Yang, L; Morriello, G; Nargund, R; Patchett, A A; Howard, A D. (1999). Growth hormone releasing substances: types and their receptors.. Hormone research, 51 Suppl 3, 1-8.