Kisspeptin

Overview

Kisspeptin is a naturally occurring neuropeptide encoded by the KISS1 gene that serves as the master regulator of the reproductive hormone axis. It is the upstream trigger of GnRH (gonadotropin-releasing hormone) release, controlling LH and FSH secretion. Clinical research has explored its use in fertility treatment, diagnosing puberty disorders, and as a potential IVF adjunct.

Mechanism of Action

Kisspeptin binds the KISS1R (GPR54) receptor on GnRH neurons in the hypothalamus, triggering pulsatile GnRH release. This activates the downstream LH and FSH cascade from the anterior pituitary, driving gonadal steroid production (testosterone, estrogen). Kisspeptin is the key gatekeeper of pubertal onset and reproductive function.

Evidence Base

Multiple human clinical studies at Imperial College London and other centers have demonstrated kisspeptin's ability to stimulate LH/FSH release in healthy volunteers and infertility patients. Phase II trials have explored its use as an IVF trigger. Published in JCI, JCEM, and Lancet Diabetes & Endocrinology.

Safety Considerations

Naturally occurring endogenous peptide with a well-understood physiological role. Clinical trial safety data exists from multiple research groups. Short half-life limits sustained effects. No FDA-approved therapeutic formulation, but the strong endogenous safety profile and clinical trial experience provide reasonable confidence.

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