Who discovered ghrelin? Masayasu Kojima, Kenji Kangawa and their colleagues identified it in 1999 at Japan's National Cardiovascular Center Research Institute. They found the hormone in rat stomach tissue while looking for a missing growth-hormone signal. Its familiar description as the “hunger hormone” came from later appetite research.
The route there took several teams and decades. Cyril Bowers helped develop synthetic peptides that released growth hormone. Merck scientists identified the receptor those compounds activated. Kojima and Kangawa's team then found the body's own matching hormone.
Cyril Bowers and the problem that came first
The early question was how to prompt the pituitary, a small gland beneath the brain, to release growth hormone. That hormone helps regulate growth and metabolism, the body's handling of energy.
At Tulane University, Bowers worked with Frank Momany and other collaborators on synthetic peptides, short chains of protein building blocks. They developed growth-hormone-releasing peptides, shortened to GHRPs. A secretagogue is simply a substance that prompts a cell to release something.
Their 1984 Endocrinology paper described the six-building-block peptide now called GHRP-6. It prompted growth-hormone release in laboratory tests and several animal species. The researchers had made a useful experimental tool before knowing which natural signal it resembled.
Bowers's 2012 history chapter explains the next question. Comparisons with growth hormone-releasing hormone, or GHRH, suggested that these synthetic peptides used a different pathway. GHRH is the brain's own signal for growth-hormone release; its separate discovery belongs to the two GHRH teams' story.
The Merck team found a receptor without its hormone
A receptor is a protein a cell uses to recognize a signal. In this case, scientists could activate it with synthetic compounds before they knew its natural partner.
Andrew Howard and colleagues at Merck Research Laboratories in Rahway, New Jersey, supplied a key piece in 1996. Their Science paper, published August 16, reported cloning the receptor from swine and human tissue. Cloning here means identifying its genetic instructions so researchers could make and study it.
The paper located the receptor in the pituitary and hypothalamus, the brain's hormone-control region. It supported the idea that the synthetic compounds copied an undiscovered hormone. Scientists now had a way to test tissue extracts for that missing signal.
That receptor is now known as the ghrelin receptor. It is the same target that explains ipamorelin's place in CJC-1295/ipamorelin combinations today. CJC-1295 copies the separate GHRH signal. The historical connection explains the mechanism; it doesn't establish a health benefit from a blend.
Who discovered ghrelin in the 1999 Nature paper?
Kojima and Kangawa's team found the natural partner in the stomach. Their finding connected a digestive organ with a pathway scientists had been studying for growth-hormone release.
The Nature paper appeared December 9, 1999. Its six authors were Masayasu Kojima, Hiroshi Hosoda, Yukari Date, Masamitsu Nakazato, Hisayuki Matsuo and Kenji Kangawa. The listed lead affiliation was the National Cardiovascular Center Research Institute in Suita, Osaka, Japan.
They purified ghrelin from rat stomach tissue and identified a chain of 28 amino acids, the building blocks of proteins. A small fatty-acid attachment on the third building block was essential for activating the receptor in their tests. The paper also described human ghrelin, which differed from the rat form at two positions.
The name came from “ghre,” an ancient language root meaning “grow.” It reflected the growth-hormone finding rather than the appetite nickname people use now.
Kojima later described the work in his firsthand account in Regulatory Peptides, published in the January 2008 issue. His account makes clear that the discovery was a search for the receptor's natural partner.
Recognition belongs to the documented work
Kangawa received the 2009 Keio Medical Science Prize. The prize body's announcement specifically credited ghrelin alongside his discoveries of other biologically active peptides and their clinical applications.
That award recognized a broader body of work. Credit for the original ghrelin paper still belongs to its six authors. Bowers's earlier peptides and the Merck receptor work supplied separate steps that made the final finding possible.
What came of it: understanding ipamorelin
Ipamorelin's history actually overlaps the search rather than starting after it. Raun and colleagues at Novo Nordisk published its defining European Journal of Endocrinology study in November 1998, a year before ghrelin's paper.
Ipamorelin is an agonist, meaning a substance that activates a receptor. The 1998 work showed growth-hormone release through the pathway later identified with ghrelin. Its findings came from rat pituitary cells, rats and pigs, with the hormone-selectivity tests done in pigs, rather than a trial establishing long-term safety in people.
Human work did follow. A 1999 study in Pharmaceutical Research tested five infusion rates, with eight healthy men at each level. It measured ipamorelin levels and growth-hormone responses. That was a study of how the compound behaved in people, rather than a recovery or aging trial.
Modern pairings put ipamorelin alongside a different signal. Tesamorelin/ipamorelin pairs the ghrelin-receptor approach with a modified version of GHRH. The sermorelin and ipamorelin comparison explains the two receptor families in more detail.
The hunger hormone discovery went beyond growth hormone
The appetite role wasn't just a new name for the original experiment. It required its own evidence.
In a 2001 Journal of Clinical Endocrinology & Metabolism study, Wren and colleagues tested ghrelin against saline in nine healthy volunteers. Participants consumed about 28% more energy from a buffet during ghrelin infusion. That was an acute human feeding experiment, not a long-term weight-management study.
As of October 1, 2026, the day this article was written, the September 2026 issue of Metabolism includes a human study linking ghrelin levels with food intake three hours later. Published online June 24, it varied the protein and energy content of meals across four test days. Researchers measured hormones; they did not give participants ghrelin or ipamorelin. The result adds evidence about appetite signals without establishing a treatment effect.
What this history cannot promise
Finding a receptor and its natural hormone explains how a pathway works. It doesn't show that activating it produces better sleep, faster recovery or longer life.
Ghrelin and ipamorelin are different molecules, even though they act on the same receptor. A finding about hunger during ghrelin infusion cannot supply an appetite estimate for ipamorelin. Animal findings also cannot supply long-term safety results for people.
The ipamorelin evidence guide covers the later compound studies. Each study still needs to be judged by what it measured, who participated and which formulation was tested.
Where a prescription fits today
Promise's CJC-1295/ipamorelin formulation is offered by prescription after a licensed provider reviews your request; it is a compounded medication and is not FDA-approved. Its tesamorelin/ipamorelin formulation, coming soon (add me to the list), will also be compounded, which is different from an FDA-approved product: the formulation Promise will offer is not FDA-approved. FDA explains that compounded drugs do not undergo its review for safety, effectiveness or quality before marketing.
A licensed provider may still prescribe a compounded formulation; that decision is between the patient and the doctor. At Promise, a licensed provider reviews every request, and not everyone qualifies.
A prescription route connects the decision with a clinician and dispensing with a licensed U.S. compounding pharmacy. The discovery explains why these molecules attract interest. The visit is where that interest meets a person's medical history.
