Kisspeptin

Hypothalamic peptide encoded by the KISS1 gene; a master regulator of GnRH secretion and reproductive function.

Overview

Kisspeptin is the collective name for peptides derived from the KISS1 gene product, which signals through the G protein-coupled receptor GPR54 (KISS1R). The best-known form is kisspeptin-54 (also called metastin), with shorter bioactive forms such as kisspeptin-10 sharing the same receptor. Kisspeptin is now recognized as a central regulator of the reproductive axis: it sits upstream of GnRH neurons and gates the onset of puberty and adult gonadotropin secretion. Human infusion studies have confirmed dose-dependent stimulation of LH release.

Mechanism

Kisspeptin neurons in the hypothalamus relay metabolic, circadian, and steroidal signals to GnRH neurons, which express the kisspeptin receptor. Receptor activation depolarizes GnRH neurons and triggers GnRH release, which then drives pituitary LH and FSH secretion. Loss-of-function mutations in KISS1 or KISS1R cause hypogonadotropic hypogonadism in humans, demonstrating the pathway's necessity for reproductive function.

Dosing

Published human research has used intravenous bolus or short infusions of kisspeptin (commonly kisspeptin-54) in dose-escalation studies in healthy volunteers and in specific patient groups. Dosing in rodent work is typically by injection at microgram-per-kilogram amounts per protocol. All figures should be taken from the primary literature.

Expected Effects

dose-dependent release of LH and, secondarily, FSH in human infusion studies
restoration of gonadotropin pulsatility in some hypogonadal states in research settings
use as a diagnostic probe of hypothalamic-pituitary-gonadal function in ongoing studies

Side Effects & Tolerability

Human research infusions have generally been well tolerated, with flushing at higher doses the most commonly reported effect. Long-term safety data are limited, and the peptide has not been approved as a therapeutic agent.

Storage

Lyophilized kisspeptin should be stored desiccated, protected from light, and kept frozen at -20 deg C or below. After reconstitution, solutions should be refrigerated at 2-8 deg C and used within a short period, avoiding repeated freeze-thaw cycles.