Kisspeptin-10 · UK research stock

Most research interest sits in the hypothalamic-pituitary-gonadal axis. Kisspeptins were identified in 2001 as the natural ligands of GPR54, and the KISS1/GPR54 system has since been described as a gatekeeper of GnRH neurons, involved in their activation at puberty and their regulation by gonadal steroids. The mechanism studied is receptor activation on GnRH neurons, driving GnRH release and downstream luteinising hormone secretion. Rat work has used intra-arcuate and intra-preoptic administration to test whether kisspeptin-GPR54 signalling in the arcuate nucleus sets GnRH pulse generator frequency. A separate line of work follows the original metastasis-suppressor role, including effects on cell migration in receptor-transfected lines.

The evidence base spans cell assays, rodent studies and small human infusion studies. First-in-human studies examined dose dependency and the time course of LH stimulation after intravenous kisspeptin-10, comparing it with GnRH. Enhanced LH pulsatility has also been reported in hypothalamic amenorrhoea, in hypogonadal men with type 2 diabetes, and in neurokinin B signalling defects. Findings are not uniform: an acute injection delayed the next endogenous LH pulse in men, but the same protocol did not show resetting of the pulse generator in women. It is an unapproved investigational peptide with no licensed product.

The peptide is cleared quickly, and its short circulating life is the reason continuous infusion protocols exist alongside bolus work. Continuous administration has produced a sustained LH rise that then declines towards the end of the infusion, a pattern relevant to receptor desensitisation studies.