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From Cancer Gene to Puberty Switch: The Kisspeptin Story, and Why It Is Named After Chocolate
Few peptide names are as playful as kisspeptin. It was not named for the kind of kiss you might expect. It was named for a chocolate candy, because the laboratory that found it was in Hershey, Pennsylvania. The story that follows, from a cancer gene to the switch that starts puberty, is one of the best examples of how biology surprises its investigators.
Key takeaways
- In 1996 a team at the Penn State Hershey Medical Center reported KiSS-1, a gene that suppresses the spread of melanoma cells.
- The name plays on Hershey’s Kisses; the SS stands for suppressor sequence.
- In 2001 several groups showed that the gene codes for peptides that activate an orphan receptor, GPR54.
- In 2003 two groups found that people with mutations in GPR54 fail to go through puberty.
- Kisspeptin neurons in the hypothalamus stimulate GnRH release, as in the Knobil story.
A tumor suppressor in a chocolate town
The first paper came from the laboratory of Danny Welch, who was searching for genes that stop cancer cells from forming distant tumors. He identified a human gene that, when added to melanoma cells, reduced their ability to spread in animal models. Colleagues playfully named it KiSS-1, after the famous local candy, with SS standing for suppressor sequence.
The peptide emerges
The gene’s product was not at first well understood. In 2001 several groups, working from different directions, found that the gene encoded a precursor that is cut into peptides, the longest of which has 54 amino acids and shorter fragments of 10 to 14. These peptides bound to an orphan receptor then called GPR54. Because they came from KiSS-1 they were named kisspeptins. As in the story of orexin, an orphan receptor and a hunt for its partner brought a peptide into view.
The puberty twist
In 2003, two teams, one in Boston led by Stephanie Seminara and William Crowley, and one in France led by Nicolas de Roux, studied families in which several people did not go through puberty. They found mutations in the gene for GPR54. Without a working receptor, the brain’s signal to the reproductive system never reached the level needed. A peptide that had been studied as a tumor suppressor turned out to be a gatekeeper for puberty.
How it works
Kisspeptin neurons sit in the hypothalamus and stimulate the nerve cells that release GnRH, which in turn drives the pituitary. They respond to signals about energy balance, season and sex hormones. In research models, kisspeptin is among the most potent known activators of the reproductive axis. The pulse pattern matters, in line with the principles in our desensitization post.
Lab notes
- Kisspeptin has a family of fragments, so sequence and length must be stated.
- Peptides with amides at the end need careful identity checks, as in terminal modifications.
- Responses are measured in receptor assays such as functional assays and binding assays.
- Short fragments are broken down fast, as in stability assays.
The bottom line
Kisspeptin is a reminder that a molecule’s first name is rarely its last job. A cancer suppressor, named for candy, became a key to understanding puberty. See more peptide history in our history of peptide drugs.
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For laboratory research use only. Not for human or veterinary use, and not intended to diagnose, treat, cure or prevent any condition. This article is educational and is not medical advice.