Biology Reference
In-Depth Information
Table 4.3
Summary of effects of acute administration of kisspeptin-10, -52, and -54 on LH
secretion in the rat
Peptide Route Dose range Effect on LH References
Kiss 10 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
]
Kiss 52 ICV 0.1 nmol 50× inc [
47
]
IV 1-10 nmol/kg 4-14× inc [
8
,
47
]
Kiss 54 SC 0.1-50 nmol 5-32× inc [
1
,
2
]
ICV
intracerebroventricular;
IP
intra-peritoneal;
IV
intravenous;
SC
subcutaneous;
IC
intracardiac;
Inc
increase in plasma levels
sheep, termed “murine kisspeptin-10,” is one amino acid different from the sequence
of human kisspeptin-10. Horse kisspeptin-10 is one further amino acid different
from rodent, pig, cow, and sheep kisspeptin-10 [
44
]. Kisspeptin-10 is simpler and
cheaper to synthesize when compared with kisspeptin-54; therefore more studies
use kisspeptin-10 than kisspeptin-54 (or kisspeptin-52 in rodents). The plasma half-
life of kisspeptin-54 is 27.6 min, whereas the in vivo plasma half-life of kisspeptin-
10 is much shorter, at ~4 min in humans [
7
,
45
]. Kisspeptin-10 is the minimum
sequence required for activation of the kisspeptin receptor and is common to the
C-terminus of all kisspeptin isoforms [
46
]. However, this difference in half-lives
may result in a different time-profi le for activation of the kisspeptin receptor and
hence differences in gonadotropin release (Table
4.3
).
Central bolus administration of murine kisspeptin-52 and human kisspeptin-10
was compared in adult male C57BL/6 mice. Murine kisspeptin-52 stimulated LH
release from a baseline of 0.2-3.1 ng/mL at 30 min, compared to an LH release of
2.8 ng/mL after human kisspeptin-10 [
3
]. In another study, an IV dose of kiss-
peptin-10 was compared with an equimolar dose of full-length kisspeptin (rat
kisspeptin-52) in adult Sprague Dawley male rats [
8
]. Kisspeptin-10 elicited a
robust plasma LH burst, with levels peaking at 15-30 min after injection and return-
ing to baseline by 75-90 min; in contrast, the effects of kisspeptin-52 lasted longer,
being still detectable at 120 min post-injection. Consequently, the overall magni-
tude of total LH secretion following kisspeptin-52 was greater when compared with
kisspeptin-10 [
8
]. Another report in male rats compared the effects of an IV bolus
of 10 nmol/kg of rat kisspeptin-52, rat kisspeptin-10, or human kisspeptin-10; all
three isoforms resulted in peak plasma LH levels at 30 min. However, whereas rat
kisspeptin-52 increased plasma LH levels to a peak of ~2.8 ng/mL, returning to
baseline by 2 h, rat and human kisspeptin-10 both had shorter-lasting effects, with
plasma LH returning to baseline levels by 1 h (both increased plasma LH levels to
a similar peak of ~2 ng/mL) [
47
]. Hence, human and murine kisspeptin-10 have
nearly identical effects on LH secretion when given IV, and both elicit a smaller and
shorter-lasting LH response than IV kisspeptin-52. Likewise, in Corriedale ewes,
murine kisspeptin-10 stimulates gonadotropin secretion to the same degree as
human kisspeptin-10 [
25
].
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