Kisspeptin-10

Kisspeptin-10 is a way to switch on the hormone axis between hypothalamus, pituitary and gonads on demand. The decapeptide is the shortest biologically active piece of the KISS1 gene product; the long form, kisspeptin-54, carries the same ten amino acids at its C-terminus. The short length makes synthesis easier and characterization cleaner.

The mechanism is well described: the peptide binds the receptor GPR54 (also called KISS1R) on the GnRH neurons of the hypothalamus. The result is a strong release of GnRH, to which the anterior pituitary responds with LH and FSH. The kisspeptin family was discovered in the early 2000s as an upstream controller of the reproductive axis, a finding that reshaped reproductive endocrinology.

Three observations that turned the peptide into a standard tool:

• In 2001 the kisspeptins (54, 14 and 13 amino acids long) were recognized as the body's own binding partners of GPR54, a receptor that until then had no known ligand.
• Mutations in the GPR54 gene leave humans and mice with hypogonadotropic hypogonadism; without a working receptor, puberty does not start.
• In healthy men, a single intravenous bolus produced a fast, dose-dependent LH surge; under a continuous infusion, testosterone rose along with the number and height of LH pulses. In women the response depended on the cycle phase: LH and FSH rose in the preovulatory phase but not in the follicular phase.

In research, kisspeptin-10 therefore serves above all to probe the regulation of the reproductive axis.

Kisspeptin-10 is described as well tolerated in studies, but it acts directly on the hormone axis. What you should keep in mind:

• Hormonal effect: the rise in GnRH, LH and FSH is not a side effect but the core of the action; shifts in reproductive hormones are to be expected.
• Injection site: mild redness or a feeling of pressure is the most common local observation.
• Circulation: a brief sensation of warmth or mild dizziness right after dosing is mentioned occasionally.
• Short half-life: the peptide is broken down quickly, which makes steering the effect in systemic experimental setups harder.
• Data situation: human studies are limited to short-term endocrine endpoints; long-term data hardly exist.

This summary is no substitute for medical advice.

• The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54 - the paper that identified kisspeptins as ligands of GPR54.
• The GPR54 gene as a regulator of puberty - receptor mutations prevent normal puberty in humans and mice.
• Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men - human study on LH rise, testosterone and LH pulses after bolus and infusion.
• The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans - shows that the hormone response in women depends on the cycle phase.