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Fig. 5.1 Effects of acute exposure to kisspeptin-10 in healthy men and women. A single intrave-
nous bolus of kisspeptin-10 0.24 nmol/kg was given to ( a ) healthy men ( n = 13) and healthy women
in the ( b ) early follicular ( n = 10), ( c ) late follicular/preovulatory ( n = 3; note different Y -axis scale),
and ( d ) mid-luteal ( n = 14) phases of the menstrual cycle, with LH measured every 10 min 6 h
before and 6 h after kisspeptin administration. Each point indicates the mean LH (±SEM) across
all subjects at each time point. Arrows indicate the time of kisspeptin administration. Adapted with
permission from refs. [ 11 , 31 ]
than those of endogenous pulses, but there was overlap between the ranges. Thus,
the kisspeptin-10 dose of 0.24 nmol/kg produced physiologic to slightly supraphysi-
ologic LH responses. Given the data from dose-response studies described above,
which showed that a dose of 0.24 nmol/kg is near the plateau of the dose-response
curve, this result suggests that, in men, endogenous kisspeptin “drive” lies only
slightly below the threshold required for maximal stimulation of GnRH secretion.
Changes in Kisspeptin Responsiveness Across the Menstrual
Cycle in Healthy Women
Studying the effects of kisspeptin in women adds a layer of complexity: the changes
in neuroendocrine activity and sex-steroid production across the menstrual cycle [ 30 ].
Even more so than in men, various isoforms of kisspeptin and modes of administra-
tion have been used in women, resulting in different durations of exposure to kiss-
peptin. These studies have revealed marked variation in the responses to kisspeptin
across the menstrual cycle.
The effects of very brief exposure to kisspeptin have been studied in women in two
studies that delivered kisspeptin-10 as single intravenous boluses (Fig. 5.1 ) [ 14 , 31 ],
which (as noted above) produce a rapid and brief rise in kisspeptin immunoreactivity
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