Peptide Hormones Explained: From Insulin to GLP-1

Hormones are the body’s long-distance messages, and a large share of them are peptides. Insulin, glucagon, GLP-1, growth hormone-releasing hormone, oxytocin, parathyroid hormone: all are chains of amino acids released into the blood to tell distant cells what to do. They were also among the first molecules biology ever decoded.

This guide explains what peptide hormones are, how they differ from steroid hormones, how they work, and gives a reference table of the major ones, linked to our research guides.

The short answer

• Peptide hormones are hormones made of amino-acid chains, released into the blood by glands and specialized cells to act on distant tissues.
• They are made as larger precursors, stored in secretory granules and released on demand, unlike steroid hormones, which are made from cholesterol and released as they are produced.
• Because they cannot cross cell membranes, they act on receptors at the cell surface, most often G protein-coupled receptors. Insulin is a notable exception, with an enzyme-linked receptor.
• The first hormone ever discovered, secretin, in 1902, is a peptide, and insulin, in 1922, was the first peptide medicine.
• Many research peptides are hormones, fragments of hormones or engineered analogues of them.

Peptide, steroid and amine hormones

How peptide hormones work

A peptide hormone’s life follows a pattern. It starts as a longer precursor protein, which enzymes trim into the active hormone, sometimes adding finishing touches such as an amide cap or, in ghrelin’s case, a fatty-acid chain. The finished hormone is packed into granules and released when the cell receives the right signal, such as rising blood sugar for insulin.

In the blood it travels freely and is usually broken down within minutes, which keeps signals short and sharp. At its target it binds a surface receptor, most often a GPCR, which relays the message inside the cell; our guide to how peptide receptors work explains that step. Most hormone systems are also regulated by feedback. Growth hormone-releasing hormone, for example, triggers growth hormone, which raises IGF-1, which in turn damps the system down. Many are released in pulses, and the pattern can matter as much as the amount.

The major peptide hormones

Two patterns stand out. The class B receptor hormones, from GHRH to glucagon to secretin, are related in sequence and size. And the hypothalamus sits at the top of several hormone chains, releasing short peptides such as TRH and GnRH that control the pituitary.

A short history

1. 1902William Bayliss and Ernest Starling discover secretin, a gut peptide that switches on the pancreas through the blood, the first hormone ever identified. Starling coins the word “hormone” in 1905.
2. 1922Insulin, extracted at the University of Toronto, becomes the first peptide hormone used as a medicine. See Canada’s century of peptide discovery.
3. 1953Vincent du Vigneaud synthesizes oxytocin, the first peptide hormone made in a lab.
4. 1955Frederick Sanger completes the amino-acid sequence of insulin, the first protein ever sequenced, and later receives the 1958 Nobel Prize.
5. 1977Roger Guillemin and Andrew Schally share a Nobel Prize for identifying the hypothalamus’s peptide hormones, with Rosalyn Yalow, whose radioimmunoassay made it possible to measure them.

From hormones to analogues

Natural peptide hormones are short-lived, which is useful for the body but awkward for researchers and drug developers. Much of modern peptide chemistry turns them into longer-lasting analogues: semaglutide from GLP-1, tesamorelin from GHRH, octreotide from somatostatin, leuprolide from GnRH and teriparatide from the first 34 residues of PTH. Our guide to how peptides are made to last explains the chemistry. Many research peptides follow the same pattern: sermorelin is the active fragment of GHRH, kisspeptin-10 the active tail of the kisspeptins, and GHRPs and ipamorelin are synthetic ghrelin-receptor agonists.

Frequently asked questions