KISS1KISS1R

KISS1KISS1R refers to the kisspeptin signaling system, comprising the KISS1 gene and its receptor KISS1R (also known as GPR54). The system is best known for regulating reproductive maturation and GnRH release, but the genes were originally described in cancer biology as metastasis suppressors before their key role in puberty was understood.

KISS1 encodes a 145-amino-acid precursor that is proteolytically processed into several active peptides, collectively called kisspeptins. The principal products include kisspeptin-54 (KP-54, metastin), kisspeptin-14, kisspeptin-13, and kisspeptin-10. Among these, KP-54 is the longest and widely studied. Kisspeptins circulate and act as ligands for KISS1R, with biological activity dependent on proper processing and peptide integrity.

KISS1R is a G protein-coupled receptor expressed in the hypothalamus, particularly on neurons that produce gonadotropin-releasing hormone (GnRH), as well as in several peripheral tissues. Binding of kisspeptins to KISS1R activates Gq/11 signaling, leading to phospholipase C activation, increased intracellular calcium, and stimulation of GnRH neuron firing. This, in turn, promotes pulsatile GnRH secretion and downstream luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from the pituitary.

Physiological roles include initiation of puberty and maintenance of reproductive function, with kisspeptin signaling modulated by sex steroids and energy balance. Clinically, mutations in KISS1 or KISS1R can cause congenital hypogonadotropic hypogonadism. Kisspeptin pathways are also studied for potential fertility therapies and, in cancer biology, KISS1 family members have been described as metastasis suppressors in some contexts. The system is conserved across vertebrates and continues to be a focus of endocrinology and cancer research.