madman
Super Moderator
* Within the arcuate nucleus, a specialized subset of kisspeptin neurons, known as KNDy (Kisspeptin/Neurokinin B/Dynorphin) cells, functions as a “pulse generator,” coordinating rhythmic bursts of activity that drive the pulsatile release of GnRH [3, 4].
* Three healthy adult men received a continuous intravenous infusion of kisspeptin-10 at a dose of 12.5 mcg/kg/h for 24 hours
* 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.
* nAs previous studies have varied in the isoform of kisspeptin used and their pharmacokinetics[50, 51], it is important to remember that kisspeptin-10 and − 54 may differ with respect to thresholds for receptor saturation and desensitization.
* In summary, while our study reinforces previous observations that kisspeptin-10 infusion initially stimulates the hypothalamic-pituitary-gonadal axis, it remains unclear whether prolonged exposure duration will attenuate kisspeptin receptor signaling in eugonadal male. Modulation of kisspeptin receptor signaling in humans is likely to be both time- and dose-dependent.
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 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.
Introduction
Kisspeptin plays a central role in GnRH secretion and is thus considered a key regulator of reproductive function. Within the arcuate nucleus, a specialized subset of kisspeptin neurons, known as KNDy (Kisspeptin/Neurokinin B/Dynorphin) cells, functions as a “pulse generator,” coordinating rhythmic bursts of activity that drive the pulsatile release of GnRH [3, 4]. This finely tuned system is obligatory for normal sexual maturation, as evidenced by the consequences of genetic disruptions: loss-of-function mutations in the kisspeptin receptor (KISS1R ) [5, 6] and kisspeptin gene (KISS1 )[7, 8] are associated with hypogonadotropic hypogonadism, while gain-of-function mutations are associated with central precocious puberty[9, 10].
In summary, while our study reinforces previous observations that kisspeptin-10 infusion initially stimulates the hypothalamic-pituitary-gonadal axis, it remains unclear whether prolonged exposure duration will attenuate kisspeptin receptor signaling in eugonadal male. Modulation of kisspeptin receptor signaling in humans is likely to be both time- and dose-dependent. As previous studies have varied in the isoform of kisspeptin used and their pharmacokinetics[50, 51], it is important to remember that kisspeptin-10 and − 54 may differ with respect to thresholds for receptor saturation and desensitization. Our study was designed as a proof-of-concept experiment to definne the physiological response to sustained kisspeptin exposure, which can inform future studies.
* Three healthy adult men received a continuous intravenous infusion of kisspeptin-10 at a dose of 12.5 mcg/kg/h for 24 hours
* 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.
* nAs previous studies have varied in the isoform of kisspeptin used and their pharmacokinetics[50, 51], it is important to remember that kisspeptin-10 and − 54 may differ with respect to thresholds for receptor saturation and desensitization.
* In summary, while our study reinforces previous observations that kisspeptin-10 infusion initially stimulates the hypothalamic-pituitary-gonadal axis, it remains unclear whether prolonged exposure duration will attenuate kisspeptin receptor signaling in eugonadal male. Modulation of kisspeptin receptor signaling in humans is likely to be both time- and dose-dependent.
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 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.
Introduction
Kisspeptin plays a central role in GnRH secretion and is thus considered a key regulator of reproductive function. Within the arcuate nucleus, a specialized subset of kisspeptin neurons, known as KNDy (Kisspeptin/Neurokinin B/Dynorphin) cells, functions as a “pulse generator,” coordinating rhythmic bursts of activity that drive the pulsatile release of GnRH [3, 4]. This finely tuned system is obligatory for normal sexual maturation, as evidenced by the consequences of genetic disruptions: loss-of-function mutations in the kisspeptin receptor (KISS1R ) [5, 6] and kisspeptin gene (KISS1 )[7, 8] are associated with hypogonadotropic hypogonadism, while gain-of-function mutations are associated with central precocious puberty[9, 10].
In summary, while our study reinforces previous observations that kisspeptin-10 infusion initially stimulates the hypothalamic-pituitary-gonadal axis, it remains unclear whether prolonged exposure duration will attenuate kisspeptin receptor signaling in eugonadal male. Modulation of kisspeptin receptor signaling in humans is likely to be both time- and dose-dependent. As previous studies have varied in the isoform of kisspeptin used and their pharmacokinetics[50, 51], it is important to remember that kisspeptin-10 and − 54 may differ with respect to thresholds for receptor saturation and desensitization. Our study was designed as a proof-of-concept experiment to definne the physiological response to sustained kisspeptin exposure, which can inform future studies.
