Kisspeptin — 5mg

Kisspeptin is the product of the KISS1 gene and acts as the primary upstream regulator of gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. Its discovery reshaped reproductive endocrinology: before kisspeptin was characterized, the mechanism that triggered puberty and controlled GnRH pulsatility throughout reproductive life was largely unknown. Loss-of-function mutations in KISS1 or its receptor (KISS1R/GPR54) produce hypogonadotropic hypogonadism and failure to undergo puberty, definitively establishing the peptide's role as the master switch of the reproductive axis.

At the receptor level, kisspeptin binds KISS1R on GnRH neurons in the preoptic area and arcuate nucleus, triggering Gq-coupled signaling cascades that depolarize the neurons and drive pulsatile GnRH secretion. The pulsatility pattern — not just the absolute GnRH level — determines downstream LH and FSH release from the pituitary, which in turn governs ovarian or testicular function. Two anatomically distinct kisspeptin neuron populations manage different aspects of this axis: the arcuate population is responsible for negative feedback-driven pulsatility, while the preoptic population mediates the preovulatory LH surge in females.

Research applications have expanded well beyond the initial reproductive endocrinology focus. Kisspeptin has been investigated as a fertility-restoring agent in hypothalamic amenorrhea, as an alternative to hCG triggers in IVF protocols (where it produces ovarian hyperstimulation syndrome less frequently), and as a diagnostic probe for reproductive axis function. Parallel lines of investigation have examined its role in metabolism-reproduction coupling — kisspeptin neurons integrate leptin signaling, connecting energy status to fertility — and in neuropsychiatric research, where KISS1R expression in limbic structures suggests roles in emotional and social processing that extend beyond classical reproductive function.