Biology Reference
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In one study, ICV administration of 0.1 nmol of murine kisspeptin-52 to male
Wistar-Imamichi rats (8-10 weeks of age) stimulated a gradual increase in plasma
LH levels from a baseline of 0.2 ng/mL to a peak of ~10 ng/mL at 2 h, which per-
sisted throughout the 3 h sampling period. However, ICV administration of the
same dose of murine or human kisspeptin-10 failed to increase plasma LH
levels [
47
]. ICV administration of 1 nmol human kisspeptin-10 increased LH levels
to ~2 ng/mL, whereas the same dose of murine kisspeptin-10 increased LH levels to
a peak of ~4.5 ng/mL at 2 h [
47
]. Hence, centrally administered rat kisspeptin-52
stimulates LH to a greater degree and for longer than either human or murine kiss-
peptin-10. Oddly, murine kisspeptin-10 has a greater effect than human kisspeptin-
10 when administered centrally at the same dose to rats, unlike when given IV. It
would be interesting to determine whether human or murine kisspeptin-10 have
higher potencies in humans or primates.
IP administrations of murine kisspeptin-10, human kisspeptin-10, murine kiss-
peptin-52, and human kisspeptin-54 were compared in adult male NMRI (Naval
Medical Research Unit) mice. Murine kisspeptin-52 was most effective in stimulat-
ing release of testosterone, followed by murine kisspeptin-10, then human kiss-
peptin-54, and fi nally human kisspeptin-10 [
48
]. It is interesting that murine
kisspeptin was more effective than human kisspeptin in stimulating testosterone
release in rodents, although the reasons for this remain unclear. Also of interest,
both murine and human kisspeptin-10 had a more rapid onset of action when com-
pared with the longer sequences of kisspeptin. Human kisspeptin-54 appeared to
have the longest duration of action, with a peak effect on free testosterone occurring
at 60 min [
48
]. Hence, it appears that shorter sequences may have a more rapid
onset of action, whereas longer sequences may have a longer duration of effect.
Recently, an analogue of kisspeptin-10, [dY]1KP-10, was developed. Although
[dY]1KP-10 has similar in vitro binding to the kisspeptin receptor, it is more potent
in vivo when given to adult male C57Bl/6 mice. IP [dY]1KP-10 increased plasma
LH and testosterone levels at 20 min post-injection to a greater degree than kiss-
peptin-10. Furthermore, at 60 min, a 0.15 nmol dose of [dY]1KP-10 signifi cantly
increased total testosterone levels, whereas the same dose of kisspeptin-10 had no
signifi cant effect [
49
]. The reason for the higher potency of the kisspeptin analogue
is not immediately clear.
Comparison of Different Routes of Administration
Remarkably, kisspeptin has been shown to be effective in stimulating gonadotropin
release when given by a number of routes of administration, including ICV, IP, SC,
and intramuscular (IM) injection. However, different routes of administration may
result in varying peak concentrations and duration of circulating kisspeptin levels;
these may, in turn, result in differential stimulation of the kisspeptin receptor. The
volume of distribution of ICV administration is smaller when compared with
peripheral administration, and kisspeptin is thought to have a central location of
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