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GHRH (Growth Hormone-Releasing Hormone): The Brain's Signal for Growth Hormone, First Found in a Pancreatic Tumour

Growth hormone-releasing hormone is a 44-amino-acid hormone from the hypothalamus that tells the pituitary to release growth hormone. It was first sequenced in 1982 from pancreatic tumours that had caused acromegaly, and two approved drugs — sermorelin and tesamorelin — are built on it.

Made by the body44 amino acids — just over the 40-residue protein lineTwo approved drugs are built on it

Caroline S · Published 2026-11-02

Length

44 amino acids ending in leucine amide (UniProt P01286, residues 32–75 of a 108-residue precursor). That is just over the 40-residue line US regulation uses for proteins (21 CFR 600.3); a 40-residue form was also isolated in 1982.

Sequence

YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2 (human GHRH 1-44; Guillemin et al. 1982 and UniProt P01286)

Origin

Released by the hypothalamus and carried to the pituitary gland (UniProt P01286). First isolated and sequenced in 1982 from human pancreatic tumours that were releasing it and had caused acromegaly (Guillemin et al., Science, PMID 6812220; Rivier et al., Nature, PMID 6292724).

Last reviewed

2026-11-02

What is it good for?

In the body, it is the hypothalamus's 'release' signal to the pituitary: UniProt's annotation states that it 'acts on the adenohypophyse to stimulate the secretion of growth hormone'. GHRH itself is not sold as a medicine in the US, but two approved drugs copy it — sermorelin (its first 29 residues, approved and later discontinued) and tesamorelin (a modified full-length analogue, approved for one narrow use in HIV-associated abdominal fat).

Illustration: A clear glass test tube with a pale green pellet on a white surface, deep green background.
Illustration

What it is

GHRH is the hypothalamus's signal to release growth hormone. It is a chain of 44 amino acids ending in an amidated leucine, cut from a 108-residue precursor (UniProt P01286, residues 32–75). At 44 residues it is just over the 40-amino-acid line US biologics rules (21 CFR 600.3) use for proteins — see the peptide-or-protein entry — and the library carries it because two of its entries, sermorelin and tesamorelin, are copies of it.

It goes by several names: GRF and GHRF (growth hormone-releasing factor, the older name), somatoliberin, and somatocrinin.

How it was found

The hormone exists in the hypothalamus in quantities too small to sequence. The breakthrough came from tumours. In November 1982 two groups independently reported growth hormone-releasing peptides from human pancreatic tumours that had caused acromegaly — the overgrowth disease of excess growth hormone:

  • Guillemin and colleagues (Science, PMID 6812220) isolated a 44-amino-acid peptide, published its full sequence, and showed the synthetic copy "has full biological activity in vitro and in vivo specifically to stimulate the secretion of immunoreactive growth hormone". They noted it was "identical in biological activity" to the still uncharacterised factor in hypothalamic extracts.
  • Rivier and colleagues at the Salk Institute (Nature, PMID 6292724) characterised a growth hormone-releasing factor from a pancreatic islet tumour, with its sequence analysis published the same month (Spiess et al., PMID 6295453).

Esch et al. (PMID 7159418) also described a 40-residue form from the same kind of tumour.

Which part does the work

The two 1982 tumour peptides were not quite the same length. Guillemin's group reported 44 residues ending in an amidated leucine; the Salk group's sequence analysis (Spiess et al., PMID 6295453) established the first 39 residues by Edman degradation and proposed that alanine at position 40, as a free acid, ended its form. The overlap is exact — the 40-residue form is the same chain stopping four residues sooner.

The same paper settled which stretch matters. Synthetic versions ending at residue 40 (free acid or amide) and a version ending at residue 29 (amide) "show equivalent in vitro activities" to the natural tumour peptide, and the authors concluded that the C-terminal end "does not appear to contribute significantly" to its potency. That 29-residue fragment is the molecule later developed as sermorelin:

Stretch Residues Sequence (human)
The active core (sermorelin) 1–29 YADAIFTNSYRKVLGQLSARKLLQDIMSR
Ends the 40-residue form 30–40 QQGESNQERGA
Completes the 44-residue hormone 41–44 RARL-NH2

Split by this library from the Guillemin (1982) sequence and UniProt P01286. Spiess and colleagues also noted, from sequence similarity, that the hormone belongs to the glucagon–secretin family of peptides, closest to the pig gut peptide PHI.

The GHRH test

Because it acts directly on the pituitary, GHRH has been used to test whether the pituitary can release growth hormone. Endocrine papers name the GHRH + arginine test among the recognised stimulation tests for adult growth hormone deficiency, alongside the insulin tolerance test, the glucagon test and macimorelin (2024 review, J Endocrinol Invest, PMID 38461479); one 2021 study used a lack of response to it as its reference standard (PMID 32335555). The same 2024 review cites "the unavailability of the GHRH all over the world" as a reason other tests are expected to replace it. A 2011 meta-analysis of 23 studies (over 1,100 patients) found several stimulation tests accurate but most assessed in only one or two studies (PMID 21856789). Interpreting any test belongs to the endocrinologist who ordered it.

What it does

Released by the hypothalamus, GHRH, in UniProt's wording, "acts on the adenohypophyse" — the front lobe of the pituitary — "to stimulate the secretion of growth hormone". It works against somatostatin, which holds growth hormone release back, and alongside the stomach hormone ghrelin, which works through a different receptor. Growth hormone then raises insulin-like growth factor 1, which carries much of its effect.

What is described How firm
Triggers growth hormone release Human and animal work since 1982; UniProt
Tumours releasing it cause acromegaly Human case material (the 1982 tumours)
Analogue tesamorelin reduces HIV-associated abdominal fat Approved indication (see its entry)
Anti-ageing or body-composition benefit in healthy adults No approval found for GHRH or either analogue

The drugs built on it

Drug What it copies FDA status (openFDA Drugs@FDA, 2026-11-02)
Sermorelin (Geref) GHRH 1–29 NDA019863 and NDA020443, both listed as discontinued
Tesamorelin (Egrifta) modified GHRH 1–44 BLA022505, prescription

The research-market compound CJC-1295 is also a modified GHRH 1–29 and is not approved. GHRH itself is not an approved US medicine.

Where it stands

  • Not a medicine itself; the template for two approved drugs, one now discontinued.
  • Research volume: 4,541 PubMed records for growth hormone-releasing hormone or GHRH in the title or abstract, 263 indexed as randomised trials; ClinicalTrials.gov lists 452 studies under the full name and 59 under "GHRH" (searched 2026-11-02).

Somatropin is the growth hormone GHRH releases, and MK-677 a non-peptide that raises it by the ghrelin route instead.

What the research shows

Stimulates growth hormone release from the pituitary

Guillemin 1982 (PMID 6812220): the synthetic replicate had 'full biological activity in vitro and in vivo'; UniProt P01286 function annotation

Tumours releasing it can cause acromegaly

Both 1982 isolations (PMID 6812220, 6292724) came from human pancreatic tumours that had caused acromegaly

An analogue reduces HIV-associated abdominal fat

Tesamorelin (Egrifta, BLA022505), approved for that use only — see its entry

Raises growth hormone for anti-ageing or body-composition benefit in healthy adults

Not an approved use of GHRH or either analogue; this entry found no approval for it

Bars show how much of the evidence is in humans, not how well anything works.

Where it stands

In the body

A hypothalamic hormone of the glucagon–secretin peptide family (Spiess et al. 1982) that triggers growth hormone release (UniProt P01286).

As a medicine

GHRH itself is not an approved US medicine. Sermorelin (Geref, NDA019863 and NDA020443) is listed as discontinued; tesamorelin (Egrifta, BLA022505) is a prescription drug (openFDA Drugs@FDA, 2026-11-02).

Published record

PubMed returns 4,541 records for growth hormone-releasing hormone or GHRH in the title or abstract, 263 tagged as randomised controlled trials; ClinicalTrials.gov lists 452 studies under the full name (2026-11-02).

Frequently asked questions

What is GHRH?

Growth hormone-releasing hormone: a 44-amino-acid hormone made in the hypothalamus that travels to the pituitary gland and makes it release growth hormone. It is also called GRF, GHRF or somatoliberin.

How is GHRH different from growth hormone?

GHRH is the signal; growth hormone is what the pituitary releases in response. Growth hormone (somatropin) is a 191-amino-acid protein. GHRH is 44 amino acids and acts only to trigger its release.

Is sermorelin the same as GHRH?

Sermorelin is a copy of GHRH's first 29 amino acids. It was approved as Geref; FDA's data list both its applications as discontinued. Its own entry has the details.

What is tesamorelin's relation to GHRH?

Tesamorelin is a modified version of the full 44-residue GHRH, approved as Egrifta for one use: reducing excess abdominal fat in people with HIV and lipodystrophy. Its label states it is not for weight loss.

Why was GHRH first found in a pancreatic tumour?

GHRH from the hypothalamus exists in tiny amounts. In 1982 two groups found that certain pancreatic tumours were releasing large amounts of a growth hormone-releasing factor and had caused acromegaly, which gave them enough material to sequence it. It proved identical in activity to the factor in hypothalamic extracts.