Growth Hormone Releasing Hormone Fragment 1-29 (Sermorelin Acetate /
Geref)

The Discovery

Two Scientists, Millions of Brains, and a Decades-Long Race

The fierce rivalry that led to finding the brain's growth hormone messenger

In 1961, a famous endocrinologist stood in front of a room full of scientists and mocked Roger Guillemin and Andrew Schally. He compared their search for hypothalamic hormones to hunting the Loch Ness Monster. This single moment of ridicule lit a fire that would burn for over two decades. Guillemin and Schally became rivals, then competitors, then obsessed with the same goal: finding the chemicals that the hypothalamus (a walnut-sized part of the brain) uses to control the pituitary gland (another small gland below it).

Guillemin worked at the Salk Institute in California, processing 5 million sheep hypothalami—the plural of hypothalamus—to extract tiny amounts of hormones. Schally worked thousands of miles away in New Orleans at a VA Medical Center, processing millions of pig brains for the same reason. It was grinding, unglamorous work. Guillemin's team would boil sheep brains, add chemicals, centrifuge, concentrate, and repeat. Schally's team did the same with pig brains. Both knew that hypothalamic hormones existed. Both believed they could isolate them. And both knew the other was trying to do exactly the same thing, faster.

Their competition became legendary in science. Schally had actually worked briefly in Guillemin's lab before leaving to start his own rival operation. Neither trusted the other. Neither wanted the other to win first. Scientists watched them like tennis fans watching a match. Guillemin even set up a system to alert him immediately if Schally published anything, so he could race to publish his own findings first. By 1977, their decades of work paid off: both shared the Nobel Prize in Physiology or Medicine for discovering three hypothalamic hormones: TRH (thyrotropin-releasing hormone), GnRH (gonadotropin-releasing hormone), and somatostatin. It was a shared victory that neither man truly wanted to share.

But they had NOT found the growth hormone releasing hormone yet. That was the missing piece. That was the hormone that would make their stories legendary. Scientists knew it existed—they just could not find it. The hypothalamus barely made any. You could not extract it in useful amounts from normal brains. So where would it come from? The answer came from one person's disease.

In 1982, a patient with a pancreatic tumor came to medical attention. The tumor was producing growth hormone, causing a condition called acromegaly—excessive growth of hands, feet, face, and chin. But pancreatic cells should not make growth hormone. Something was wrong with the tumor. It was not making growth hormone directly. Instead, it was making GHRH—growth hormone releasing hormone—that traveled through the blood to the pituitary, telling it to pump out growth hormone. This tumor was ectopic, meaning it was making a hormone where it should not be made. But this accident, this mistake, gave Guillemin's team the gift they had been waiting for: enough GHRH to finally isolate and study.

Guillemin's team at Salk quickly extracted and purified GHRH from the tumor. They published their findings in Science in 1982: "Growth Hormone-Releasing Factor from a Human Pancreatic Tumor That Caused Acromegaly." Their key co-authors were Paul Brazeau, Charles Bohlen, Erwin Esch, and Wylie Vale. At the same moment, Wylie Vale and Jean Rivier published more detailed structural information in Nature. They showed that GHRH was 44 amino acids long. But here was the twist: they also found that you did not need all 44. The first 29 amino acids—the NH2-terminal fragment—were enough to do the job. A shortened version. A peptide. This short form became sermorelin, and it would change medicine for decades.

The Breakthrough

From Tumor Tissue to Treatment

How a synthetic hormone learned to awaken the body's own growth system

After the 1982 discovery, scientists faced a new challenge: could they make GHRH in the lab? They did not need to extract it from tumors anymore. They could synthesize it chemically. Wylie Vale and Jean Rivier at Salk proved that just 29 amino acids worked perfectly. This was huge. Shorter chains were cheaper to make, faster to synthesize, and easier to study.

Michael O. Thorner at the University of Virginia became the bridge between discovery and medicine. Thorner was not a basic scientist sitting in a laboratory processing brains. He was a clinician—a doctor who saw patients. He understood what doctors needed: a safe way to stimulate growth hormone without injecting synthetic GH into patients. Thorner knew that giving people external growth hormone came with risks. The body could become dependent. The immune system could reject it. Patients got needles every single day. What if you could just remind the body to make its own?

Thorner became obsessed with GHRH. He did something bold: he gave synthetic GHRH to normal volunteers. It worked. Their pituitary glands responded. They made more growth hormone. Then he gave it to children and adults with growth hormone deficiency. Again, it worked. Thorner realized something powerful: GHRH did not flood the body with hormone. Instead, it asked the pituitary politely. It said, "Make some growth hormone if you need to." The pituitary still had the final say. It still had control. This was gentler, smarter, more natural.

Thorner and his team designed a diagnostic test: give GHRH plus the amino acid arginine (which also boosts growth hormone), draw blood samples, and measure how much GH the pituitary produced. This became the arginine-GHRH stimulation test. It was the gold standard for diagnosing growth hormone deficiency in adults. It was elegant. It was powerful. It showed something revolutionary: the broken GH system might not be broken at all. It might just be sleeping. Wake it up with the right signal, and it would respond.

By the early 1990s, drug companies were interested. Sermorelin showed promise in children with GH deficiency. It helped them grow taller. It was safe. It had minimal side effects. The FDA reviewed the data. On September 26, 1997, the FDA approved sermorelin as Geref for treating children with growth hormone deficiency and as a diagnostic tool for GH deficiency in adults. Geref was made by EMD Serono, a company with a long history in hormone treatments. For the first time, doctors had an FDA-approved drug that asked the body to heal itself instead of replacing what was broken. It seemed like a triumph. No one knew what would come next.

The Trials

The Paradox That Made Sermorelin Perfect for Adults

Why a 'failure' in children became a triumph in grown-ups

Sermorelin had a strange paradox built into its nature. It worked beautifully—but not in the way everyone expected. For very severely growth hormone deficient children, sermorelin sometimes did not work well enough. These kids' pituitary glands had been so quiet for so long that they could not wake up fully, even with GHRH knocking at the door. They still needed external growth hormone injections. Sermorelin could not help them. This was disappointing. It felt like a failure.

But failure is sometimes just a different form of success. For adults, this "limitation" became sermorelin's greatest strength. Adults do not need as much growth hormone as growing children. They just need enough to keep their bones strong, their muscles healthy, their metabolism working right, and their sleep good. Sermorelin was perfect for this. It stimulated moderate, natural growth hormone release. It did not flood the system. It did not make patients dependent on external injections. It asked their pituitary, "Can you make a little more?" And usually, the answer was yes.

Clinicians realized sermorelin was ideal for aging adults whose growth hormone had declined. For adults recovering from illness. For athletes who wanted to boost recovery naturally. For people with metabolic problems. The diagnostic test—arginine-GHRH stimulation—became the standard way doctors tested GH deficiency in adults. It was not invasive. It was not dangerous. You got one injection, waited, got blood draws, and within hours, you knew whether your pituitary could still respond. Thousands of doctors learned the test. Hospitals added it to their protocols. Sermorelin became mainstream.

Between 1997 and 2008, Geref became trusted. Doctors knew it. Patients tolerated it well. Side effects were rare. The most common ones were mild: slight redness at injection sites, brief dizziness, or a flush of warmth. Nothing serious. Nothing that made patients stop treatment. Insurance companies covered it. Clinical data accumulated showing long-term safety. Some studies even suggested benefits beyond growth—better sleep quality, improved mood, stronger bones in aging adults.

During these eleven years, sermorelin proved itself. It was not as flashy as other hormone treatments. It did not work as fast as external GH injections. But it was smart. It was safe. It respected the body's own systems. Doctors and patients believed in it. And then, without warning, it disappeared.

Research teams continued studying GHRH and its cousins. They discovered that the brain had a second system for controlling growth hormone: ghrelin, a hormone made in the stomach that also stimulated GH release. GHRH and ghrelin worked together—a two-signal system. This led to new drug classes called GH secretagogues (drugs that make the GH system more active). Some companies explored longer-lasting versions of GHRH. Others designed stabilized versions that would not break down as fast in the bloodstream. The research showed that Thorner's basic insight was right: awakening the natural GH system was smarter than replacing it.

The Crisis

How a Manufacturing Problem Erased a Decade of Trust

The discontinuation that proved safety does not guarantee survival

On December 2, 2008, EMD Serono sent a letter to doctors and hospitals. It was short. It was devastating. They were discontinuing Geref (sermorelin). Manufacturing difficulties. Supply chain problems. Active ingredient shortages. No timeline for return. Over night, an FDA-approved, widely-used hormone drug disappeared. Doctors who had prescribed it for years suddenly could not. Patients who had stable, working treatments had to switch to alternatives. The arginine-GHRH diagnostic test became impossible to perform at most hospitals.

The FDA would later confirm in the 2013 Federal Register that Geref was "NOT withdrawn for reasons of safety or effectiveness." It was not a scandal. No patients died. No studies showed harm. It was a simple business decision: making sermorelin was hard, and it was not profitable enough for EMD Serono to keep trying. The company faced supply chain problems with the raw materials. The active pharmaceutical ingredient (API) was difficult to source. It was expensive to manufacture. Sales had become modest. The company closed the book.

For clinicians, this was a problem. The arginine-GHRH test had become standard. Hospitals had equipment set up for it. Doctors had trained staff to give it. Patients expected it. Now it was gone. Research centers could not do clinical trials requiring GHRH. Diagnostic capacity collapsed. The FDA had no backup plan. GH testing had to move to other methods that were less sensitive, less specific, or required more invasive procedures. Some hospitals used the insulin-induced hypoglycemia test—but this was dangerous and could cause real side effects. Others used glucagon stimulation tests. Nothing was as good as the arginine-GHRH test.

For patients, sermorelin disappeared into the underground. Anti-aging clinics, longevity medicine clinics, and sports medicine clinics still wanted to use it. But without an FDA-approved product, they had only one option: compounding pharmacies. These are pharmacies that mix medications from scratch, often for patients who need custom doses or forms that commercial companies do not make. Some compounding pharmacies were excellent. Others were not. Quality varied wildly. Some had strict quality control. Others had inconsistent dosing. Some had purity problems. The FDA cracked down on peptide compounders in 2013, warning them about safety and quality issues. But sermorelin compounded products remained available in a gray zone.

The loss of Geref created a vacuum. For three years, there was no FDA-approved GHRH on the market. Then, in 2010, tesamorelin arrived. This was a modified form of GHRH (the full 44-amino acid version, not the 29-amino acid sermorelin)—stabilized with a special chemical group to last longer in the bloodstream. The FDA approved tesamorelin as Egrifta for HIV-associated lipodystrophy (abnormal fat distribution in HIV patients). It was not the same as sermorelin. It was longer-acting, more stable, more expensive. It worked, but it filled a different niche. For diagnostic testing, hospitals waited for Macimorelin, an oral GH secretagogue approved in 2017. This finally brought back a diagnostic option for adult GH deficiency—but it was not the same as GHRH.

The crisis showed something harsh: an effective drug can vanish not because it fails patients, but because it fails the market. Sermorelin was safe. Sermorelin was trustworthy. Sermorelin worked. But it was not profitable, and manufacturing was hard. In the market system, that is enough to kill a drug, even when patients needed it and doctors wanted it.

The Legacy

How One Hormone Rewrote the Story of Growth

From Nobel Prize winners to peptide compounders, GHRH's impact continues to reshape medicine

The discovery of GHRH and the development of sermorelin did something remarkable: they changed how scientists thought about disease. For decades, hormone replacement meant one thing: give patients the hormone they are missing. Insulin for diabetics. Thyroid hormone for hypothyroidism. Growth hormone for short kids. But GHRH whispered a different idea: what if you could ask the body to heal itself? What if the broken system was not actually broken, but just sleeping?

This idea rippled outward. It changed how clinicians approached growth hormone deficiency in adults. It led to research on other hormone-releasing hormones. It inspired the search for secretagogues—drugs that stimulate hormone release instead of replacing the hormone itself. Today, the GH secretagogue class includes drugs like ghrelin mimetics, which activate ghrelin sensors to boost natural growth hormone. These are not GHRH, but they share the same philosophy: awaken the system, do not replace it. The ghrelin research itself came directly from understanding the GHRH system.

Tesamorelin represents GHRH's living legacy. It is a stabilized version of the full 44-amino acid GHRH, modified with a trans-3-hexenoic acid group attached to help it survive longer in the bloodstream. The FDA approved tesamorelin as Egrifta in 2010 for HIV-associated lipodystrophy—a condition where HIV medications cause abnormal belly fat despite overall weight loss. Tesamorelin stimulates GH release, which helps metabolize the excess fat. It works. More importantly, it proves that the basic GHRH concept still has clinical power: use the body's own signals to solve the problem.

Researchers have also studied tesamorelin for other conditions. The SMART trial tested it in aging adults for cognitive function and memory. While the primary results were modest, the idea persists: can GHRH or its analogs help aging brains? Can they improve quality of life? Some data suggest yes. Studies continue. Meanwhile, the peptide itself—the 44-amino acid form that Vale and Rivier sequenced in 1982—continues to inspire new analogs and modifications.

Sermorelin itself never truly disappeared. Compounding pharmacies kept making it. Anti-aging clinics kept prescribing it. The quality improved as regulations tightened. Today, sermorelin is available through compounding pharmacies for off-label uses: anti-aging, recovery from illness, metabolic support. It is not FDA-approved anymore, so patients and doctors must accept more risk. The FDA does not verify quality the way it does for standard drugs. But the demand persists because the idea is sound: a peptide that wakes up the natural growth system is better than external injections for many people.

Michael Thorner, the clinician who first gave GHRH to humans, continues research into growth hormone secretagogues. He and his collaborators are studying LUM-201, an oral GH secretagogue in development. The goal is the same as it was in 1982: find smarter ways to stimulate the body's own growth hormone system. The research that began with Guillemin's 5 million sheep brains continues in modern labs with modern tools.

The Guillemin-Schally story also endures. Their rivalry pushed science forward. Their shared Nobel Prize showed that competition and collaboration are not opposites—they are dance partners. Guillemin got the last word by discovering GHRH, but Schally's work on other hormones was equally important. Both lives mattered. Both legacies continue. Today, scientists read about their feud in textbooks and understand: great science often comes from great rivalry, great dedication, and people who refuse to accept that something is impossible.

GHRH's story teaches a final lesson: a perfect drug can disappear for imperfect reasons. Sermorelin was safe. It was effective. Patients trusted it. Doctors used it. But manufacturing became hard, and the company moved on. This happens in medicine more often than we admit. The answer is not to give up on good ideas. It is to build systems—compounding pharmacies, research, regulatory frameworks—that keep good ideas alive even when commercial viability fades. GHRH survived because the science was sound and the need was real.