Effects of Kisspeptin on Hormone Secretion in Humans - Kisspeptin Signaling in Reproductive Biology - page 90

breakdown products (such as the 9-amino acid metabolite that has been observed),
resulting in a longer apparent half-life. Without complete knowledge of the identity
and biological activity of these kisspeptin breakdown products, it is diffi cult to
know which one of these results more accurately refl ects the half-life of the bioac-
tivity of kisspeptin. Alternatively, there may be factors that prolong the half-life
of kisspeptin in vivo, such as binding of kisspeptin to binding proteins or distribu-
tion to compartments other than blood. In any case, these studies demonstrate that
the half-life of kisspeptin-10 is very short, on the order of 1-4 min.
The kinetics of the subcutaneous route of administration of kisspeptin-10
have also been examined using the same polyclonal sheep immunoassay [ 14 ].
After a single subcutaneous bolus of kisspeptin-10, kisspeptin immunoreactiv-
ity peaked at 15 min (the first time point after administration) then decayed
with a half-life of ~20 min.
Pharmacokinetics of Kisspeptin-54
The half-life of kisspeptin-54 in men has also been examined using the sheep poly-
clonal radioimmunoassay [ 13 ]. Men received an intravenous infusion of kisspeptin-54.
At the start of the infusion, kisspeptin immunoreactivity rose quickly and peaked at
30 min after the start of the infusion. After the infusion was stopped, kisspeptin
immunoreactivity decayed in a monophasic pattern with a half-life of 28 min.
The same radioimmunoassay was used to examine the pharmacokinetics of a
single intravenous bolus of kisspeptin-54 in women [ 14 ]. As expected, kisspeptin
immunoreactivity was elevated over baseline at the next time point, 10 min after IV
bolus injection. Oddly, kisspeptin immunoreactivity continued to rise gradually and
did not peak until 40 min after injection. Kisspeptin immunoreactivity then declined
gradually, but still remained detectable 3 h after injection. Because most substances
are distributed throughout the circulation within 1-2 min after IV bolus administra-
tion, at face value this observation suggests complex kinetics of kisspeptin-54. One
possibility is that kisspeptin-54 molecules formed aggregates that slowly dissoci-
ated after intravenous administration. However, a more likely explanation is that
kisspeptin breakdown products interfered with the kisspeptin immunoassay that
was used in this study.
This immunoassay has also been used to study the kinetics of the subcutaneous
route of administration of kisspeptin-54 in women, with doses ranging from 0.2 to
6.4 nmol/kg [ 15 ]. At all doses studied, kisspeptin immunoreactivity peaked at the
next time point (15 min) then declined at rates that varied by dose. At the smallest
dose (0.2 nmol/kg), kisspeptin immunoreactivity returned to baseline by 3.5 h after
injection. In contrast, after subcutaneous injection of kisspeptin-54 6.4 nmol/kg,
kisspeptin immunoreactivity was minimally decreased at the end of the 4-h study
period. Thus, kisspeptin-54 behaves as a sustained-release formulation when admin-
istered subcutaneously at high doses.