Kisspeptin-10

What Is Kisspeptin-10?

Kisspeptin-10 is a decapeptide, the shortest active fragment of the KISS1 gene product (residues 112 to 121 of kisspeptin-54), and sits at the apex of the reproductive hormone cascade. It binds the KISS1R receptor (GPR54), a G-protein-coupled receptor on GnRH neurons in the hypothalamus. KISS1R activation causes pulsatile release of gonadotropin-releasing hormone, which drives pituitary LH and FSH secretion, which in turn drives gonadal steroid production and gametogenesis.

Loss-of-function mutations in KISS1 or GPR54 cause complete failure of puberty without affecting any other pituitary function, which is how the Seminara and Crowley group at Massachusetts General Hospital established kisspeptin as the GnRH pulse generator. Kisspeptin receptors are also expressed in limbic structures (amygdala, hippocampus, cingulate, putamen), and functional imaging work from Comninos and Dhillo at Imperial College London shows kisspeptin enhances neural activity in sexual-arousal and attraction circuits independently of the hormonal response. The peptide has a plasma half-life of a few minutes and has been studied clinically as a diagnostic probe of hypothalamic function and as an ovulation trigger in IVF.