KissPeptin-10

Kisspeptin neurons in the hypothalamus (particularly in the arcuate nucleus for pulsatile GnRH regulation, and the anteroventral periventricular nucleus for the preovulatory LH surge) project directly to GnRH neurons, which express KISS1R. In research models, when kisspeptin binds KISS1R on GnRH neurons it is studied for its role in potently stimulating GnRH release. The arcuate kisspeptin neurons, which also co-express neurokinin B and dynorphin (KNDy neurons), are studied as the GnRH pulse generator — the coordinated activity associated with pulsatile GnRH secretion that underlies LH and FSH secretion in model systems.

Kisspeptin neurons receive input from leptin receptors, and leptin (the adipocyte hormone that signals nutritional adequacy) is required for normal kisspeptin neuron activity. In leptin-deficient or leptin-resistant states modelled in research, kisspeptin signaling is impaired and GnRH drive is reduced. This is studied to understand why severe nutritional restriction and extreme exercise suppress reproductive signalling in models — the body uses kisspeptin as a gate through which metabolic status must pass before reproductive function proceeds. Kisspeptin research is central to understanding how energy balance and reproduction are coupled.

The kisspeptin stimulation paradigm administers kisspeptin-10 (or kisspeptin-54) and measures LH, FSH, and testosterone/estradiol response. Unlike the standard GnRH stimulation paradigm which probes pituitary function, the kisspeptin paradigm examines the GnRH neuron and pituitary together — it tests whether GnRH neurons can respond to kisspeptin and whether the pituitary can respond to the resulting GnRH release. This allows distinction between GnRH neuron dysfunction (no response to kisspeptin) and pituitary dysfunction (response to GnRH direct stimulation but not to kisspeptin). Research groups in the UK have published kisspeptin stimulation protocols.