Kisspeptin

Kisspeptin is a family of peptide hormones encoded by the KISS1 gene. The peptides, including kisspeptin-54 (metastin) and related forms, bind to the G-protein–coupled receptor GPR54, now referred to as KISS1R. The kisspeptin/KISS1R signaling axis was first identified as a metastasis-suppressor pathway, but its primary physiological role is in the regulation of the reproductive axis.

In the hypothalamus, kisspeptin neurons stimulate the release of gonadotropin-releasing hormone (GnRH) from GnRH neurons, triggering pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. This signaling is essential for puberty, gonadal development, and fertility. In humans, loss-of-function of KISS1R or KISS1 can cause congenital hypogonadotropic hypogonadism, while disruptions in kisspeptin signaling can alter gonadotropic secretion patterns.

Anatomically, kisspeptin-producing neurons are abundant in the arcuate nucleus and the anteroventral periventricular nucleus of the hypothalamus. Distinct populations participate in estrogen feedback: arcuate kisspeptin neurons contribute to pulsatile GnRH release under negative feedback, whereas AVPV kisspeptin neurons mediate the estrogen-induced GnRH/LH surge associated with ovulation.

Clinical and research relevance: Kisspeptin signaling is explored as a target for fertility therapies, contraception, and the management of reproductive disorders. Serum kisspeptin levels rise during pregnancy and are studied as potential biomarkers of placental function and fetal well-being. Experimental kisspeptin agonists and antagonists are used to study GnRH dynamics and reproductive endocrinology.