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. When kisspeptin binds KISS1R on GnRH neurons, it potently stimulates GnRH release. The arcuate kisspeptin neurons, which also co-express neurokinin B and dynorphin (KNDy neurons), generate the GnRH pulse generator -- the coordinated activity that produces the pulsatile GnRH secretion needed for normal LH and FSH secretion.

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, kisspeptin signaling is impaired and GnRH drive is reduced, causing hypothalamic hypogonadism. This explains why severe malnutrition, anorexia, and extreme exercise suppress fertility -- 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 test administers kisspeptin-10 (or kisspeptin-54) IV or SC and measures LH, FSH, and testosterone/estradiol response. Unlike the standard GnRH stimulation test which tests pituitary function, the kisspeptin test 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 test protocols in humans.