Kisspeptin
(Metastin/Kisspeptin-54/Kisspeptin-10)

1996-2002

A Gene Named for Chocolate

Finding a Metastasis Suppressor

The story begins not with reproduction but with cancer. In 1996, researchers discovered a gene that seemed to suppress metastasis — the spread of cancer. They named it KiSS-1, playing on 'SS' for 'suppressor sequence' and 'Ki' for the lab's location in Hershey, Pennsylvania — home of Hershey's Kisses chocolates.

The peptide encoded by this gene was called kisspeptin or metastin. Scientists studied it for cancer research. But it also had a receptor — GPR54 — whose function was unknown.

No one yet realized that this playfully named molecule would prove to be reproduction's master switch.

2003

The Puberty Connection

Two Teams, One Answer

In 2003, the world changed for reproductive biology. Two research teams, working independently — Stephanie Seminara in Boston and Nicolas de Roux in Paris — studied patients who never went through puberty.

Both teams discovered that these patients had mutations in GPR54, the kisspeptin receptor. Without functional kisspeptin signaling, the brain couldn't start puberty. GnRH neurons wouldn't fire. The reproductive system stayed silent.

This was the answer to a centuries-old question: what triggers puberty? Kisspeptin signals to GnRH neurons, which then trigger the entire hormonal cascade of sexual maturation.

2003-2010

Mapping the System

Understanding the Master Switch

Scientists raced to understand kisspeptin's biology. They found that kisspeptin neurons in the hypothalamus sat upstream of GnRH neurons. When kisspeptin was released, GnRH neurons fired and the reproductive system activated.

Kisspeptin also explained other reproductive phenomena. The menstrual cycle's precise timing, the ovulation surge, the effects of stress on fertility — all involved kisspeptin signaling. It was the integration point where the brain translated signals into reproductive action.

In animals, injecting kisspeptin could trigger ovulation and restore reproductive function. The therapeutic potential was obvious.

2010-2020

Into the Clinic

Testing in Humans

Clinical trials began testing kisspeptin for fertility applications. In women undergoing IVF, kisspeptin could trigger egg maturation with potentially fewer risks than standard HCG injections. For women with hypothalamic amenorrhea (absent periods due to stress or low weight), it could restart cycles.

For men with low testosterone, kisspeptin stimulated natural hormone production. Unlike testosterone replacement, it worked through the body's own pathways, maintaining fertility and natural regulation.

Trials at Imperial College London and other centers showed promising results. Kisspeptin was safe, effective at triggering hormone release, and might offer advantages over existing treatments.

2020-Present

Expanding Applications

Beyond Basic Fertility

Research has expanded kisspeptin's therapeutic scope. Beyond fertility, it may help diagnose and treat various reproductive disorders. Kisspeptin tests can reveal how well the reproductive system functions. Treatment might help with conditions ranging from delayed puberty to polycystic ovary syndrome.

Researchers are developing longer-acting kisspeptin analogs and exploring different routes of administration. The goal is to make kisspeptin practical for everyday clinical use.

A peptide named after chocolates has become central to understanding human reproduction. From cancer research to puberty biology to fertility treatment, kisspeptin's journey shows how basic science can transform medicine.