Dynamic Modulation of LH Secretion by Continuous Kisspeptin Infusion in Healthy Men

Purpose Kisspeptin stimulates gonadotropin-releasing hormone (GnRH) release and, by extension, gonadotropin secretion. Although continuous kisspeptin administration has been shown to dampen kisspeptin-induced GnRH release in non-human primates [1, 2], this has not been replicated in the limited human studies reported to date. The objective of this study was to examine the effects of continuous kisspeptin administration on GnRH-induced luteinizing hormone (LH) secretion in healthy men. Methods Three healthy adult men received a continuous intravenous infusion of kisspeptin-10 at a dose of 12.5 mcg/kg/h for 24 hours and underwent frequent blood sampling to characterize the effect on reproductive hormones. Results Continuous administration of kisspeptin resulted in an immediate increase in LH levels, 5 to 10-fold above baseline, which were sustained for several hours. LH levels subsequently began to decline towards the end of the infusion, though they remained above baseline. Continuous kisspeptin induced a modest rise in follicle-stimulating hormone (FSH) levels. Conclusion While kisspeptin boluses have been used to probe GnRH pulse generation, continuous infusion of kisspeptin is a complementary physiologic tool to study dynamic changes in GnRH-induced LH secretion. Further studies are warranted to further elucidate the physiologic response of the kisspeptin receptor to non-pulsatile ligand administration. Clinical Trial Registration: NCT01438073 (August 24, 2011)