metastin54

Metastin-54, also known as kisspeptin-54, is a peptide hormone produced from the KISS1 gene in humans. It belongs to the kisspeptin family and binds to the G protein-coupled receptor GPR54 (KISS1R), activating GnRH neurons and stimulating the release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

The peptide is generated by proteolytic processing of a 145-amino-acid KISS1 precursor, yielding the active peptide metastin-54. Shorter forms, such as kisspeptin-14, also derive from the same precursor. The activity of kisspeptins largely depends on the C-terminal region, particularly a decapeptide that is essential for receptor activation.

The kisspeptin signaling system plays a central role in the regulation of puberty, reproduction, and fertility. It acts upstream of GnRH neurons to govern pulsatile GnRH release, and mutations in KISS1 or its receptor KISS1R can cause hypogonadotropic hypogonadism, highlighting its importance for normal pubertal development and reproductive function.

In cancer biology, KISS1 has been studied as a metastasis-suppressor gene, with kisspeptins shown to reduce metastatic potential in certain tumor models; however, the effects can be context-dependent and vary by cancer type.

Clinically, the kisspeptin–KISS1R system is explored as a diagnostic and therapeutic target. Kisspeptin stimulation tests have been used to assess pituitary-gonadal axis responsiveness, and research continues into the potential use of kisspeptin analogs for fertility treatment and cancer therapy.