Dynamic modulation of LH secretion by continuous kisspeptin infusion in healthy men

Abstract 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 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 h and underwent frequent blood sampling to characterize the effect on reproductive hormones. Results Continuous administration of kisspeptin resulted in an immediate increase in LH concentrations, from a baseline of 2.8–3.8 mIU/mL to the highest values of 17.5–30.6 mIU/mL (5- to eightfold above baseline), reached within 12–20 h of infusion onset. LH concentrations subsequently declined by 13–47% from max to end of the infusion, settling at 10.7–22.8 mIU/mL. FSH and testosterone rose modestly in parallel. Conclusion While kisspeptin boluses have been employed to probe GnRH pulse generation, continuous infusion of kisspeptin is a complementary physiologic tool used 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).