Biology Reference
In-Depth Information
Table 4.1
Summary of the effect of acute administration of kisspeptin-10 in different non-human
mammals
Species Route Dose range Effect on LH References
Rats ICV 0.1 pmol to 100 nmol 2-62.5× inc [
4
,
5
,
35
,
47
,
60
,
62
]
IP 7.5-300 nmol >10× inc [
4
,
5
,
19
]
IC 0.3-30 nmol/kg 2-8× inc [
8
]
IV 0.3 nmol to 75 nmol/kg 9-11× inc [
47
]
Mice ICV 1 fmol to 1 nmol 3-7× inc [
3
]
Hamster IP 1-7.67 nmol 3-7× inc [
61
]
Pigs ICV 7.5-75 nmol 8-14× inc [
6
]
IV 171-854 nmol 6× inc [
6
]
Sheep IV 1.6-100 nmol 2-10× inc [
25
]
Goat IV 0.77-7.67 nmol/kg 4-5× inc [
10
]
Cows IV 3.85 nmol/kg 9.7× inc [
51
]
IM 3.85 nmol/kg 3× inc [
51
]
Monkeys ICV and IV 7.67 nmol 25× inc [
9
]
ICV
intracerebroventricular;
IP
intra-peritoneal;
IV
intravenous;
IM
intramuscular;
IC
intracardiac;
Inc
increase in plasma levels
cannulae, in adult male Sprague Dawley rats stimulated LH release fourfold
following a 0.3 nmol/kg dose and eightfold following 3.0 or 30 nmol/kg doses, when
compared with pre-injection values and controls. LH secretion was stimulated
within 15 min of injection and the duration of effect of the 0.3 nmol/kg dose of
kisspeptin-10 lasted half as long (45 min) as the two higher doses. Based on this
data, the ED50 for kisspeptin-10 (the dose which caused a rise in LH in 50% of rats
given kisspeptin-10) after IV administration was calculated to be ~0.5 nmol/kg body
weight [
8
].
In 2005, Shahab et al. studied the effects of central and peripheral administration
of human kisspeptin-10 in GnRH-primed agonadal male Rhesus monkeys. The
researchers observed that 100
g kisspeptin-10 induced a signifi cant release of
gonadotropins, regardless of route of administration. For both ICV and IV treat-
ment, plasma LH levels were increased >25-fold by 30 min after the start of kiss-
peptin-10 infusion and remained elevated for ~2-3 h (Fig.
4.1
) [
9
]. A smaller ICV
dose of 30
µ
g kisspeptin-10 also stimulated LH secretion in a similar fashion.
Moreover, both the ICV and IV bolus effects of kisspeptin in this study were blocked
with GnRH antagonist treatment [
9
].
The effects of IV administration of kisspeptin were also studied in ungulates. An
IV bolus of kisspeptin-10 at doses of 1, 2.5, and 5 mg (0.77, 1.54 and 3.84
µ
mol) to
pre-pubertal gilts (female pigs) stimulated LH to a similar degree following all three
doses, whereas FSH was only signifi cantly elevated following the highest dose [
6
].
In another study, human kisspeptin-10 was administered IV to female native
Japanese goats (aged 4-5 years old) in the luteal phase, at doses of 1, 5, or 10
µ
g/kg
(0.77, 3.85 or 7.69 nmol/kg). Baseline LH levels, which were between 0.26 and
0.45 ng/mL, rose to maximal levels (1.50-1.93 ng/mL) by 20-30 min post-injection
[
10
]. In adult castrated male Shiba goats, an IV bolus of human kisspeptin-10 at a
dose of 0.38
µ
µ
mol increased pulsatile secretion of LH [
11
]. Similarly in cows, an IV
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