Kisspeptin

The upstream gatekeeper that gates GnRH pulse generation.

EndogenousEstablished

Identity

Class: RF-amide peptide (KISS1 products, e.g. kisspeptin-54/10)
Source: Hypothalamus (KNDy and AVPV neurons)
Receptor: KISS1R (formerly GPR54)

Key properties

Molecular weight

≈ 1,302.5 Da

Half-life (native)

~4–30 min (by fragment)

Model dosing

Approximate values for the native hormone. Engineered analogs are often deliberately larger and far longer-acting.

Mechanism

Kisspeptin neurons act upstream of GnRH, providing the excitatory drive that gates GnRH pulse generation. Their discovery reframed how the reproductive axis is switched on at puberty and tuned across the cycle.

Reference notes

Loss-of-function in KISS1R causes failure to enter puberty — the finding that revealed the pathway.
Kisspeptin is now seen as a key gatekeeper sitting above GnRH.
It integrates metabolic and steroid-feedback signals into the reproductive axis.

Selected literature

Curated peer-reviewed reviews, sourced from PubMed. Selected for relevance, not exhaustive — open any entry on PubMed for the full record and its primary citations.

1.The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction · Frontiers in endocrinology, 2022 · PMID 35837314
2.Pubertal development and regulation · The lancet. Diabetes & endocrinology, 2016 · PMID 26852256