Biology Reference
In-Depth Information
Effects of Development and Reproductive Maturation
on Response to Kisspeptin
Kisspeptin is thought to play an important role in pubertal development. Indeed,
inactivating mutations in the genes encoding kisspeptin or its receptor lead to hypo-
gonadotrophic hypogonadism in humans and mice [ 55 , 56 ], whereas activating
mutations lead to precocious puberty [ 57 ]. Recently, circulating plasma kisspeptin
levels were shown to be higher in central precocious puberty when compared with
normal pre-pubertal girls [ 58 ]. The onset of puberty is also known to be linked to
metabolic cues, with leptin and adipose tissue thought to be important factors in the
onset of puberty [ 59 ]. Furthermore, the effects of kisspeptin may be altered by pre-
vailing levels of sex hormones, which change with puberty. Hence, a number of
factors may result in differences in the response to exogenous kisspeptin during
pubertal maturation.
The effects of IP kisspeptin-10 on LH secretion were assessed in male and female
rats at different stages of postnatal maturation, namely the neonatal (5 day old), late
infantile (15 day old), and juvenile (25 day old) periods. IP injection of kiss-
peptin-10 at 0.75 nmol/10 g elicited greater absolute LH responses in rats in the late
infantile group (15 day old), when compared with juvenile (25 day old) and neona-
tal (5 day old) rats [ 60 ]. However, LH was stimulated to similar degrees (relative to
baseline levels) in all three stages of development. This data suggests that rats are
responsive to exogenous kisspeptin throughout development, but the pre-existing
level of activity of the reproductive axis infl uences how much gonadotropin secre-
tion is triggered following kisspeptin administration.
In hamsters, greatest sensitivity to a single IP injection of 1 nmol human kiss-
peptin-10 was observed in pubertal animals (day 45 old) when compared with
pre-pubescent (15 day) or adult (75 day) hamsters [ 25 ]. In contrast, in mice,
greater response to kisspeptin was seen in adult mice than juvenile mice. Central
administration of mouse kisspeptin-52 was carried out at doses of 10 and 100 fmol
in juvenile (day 18) and adult male C57BL/6J mice. In adults, both 10 and
100 fmol kisspeptin-54 increased plasma LH levels at 30 min post-injection [ 32 ].
However, in juvenile mice, only the 100 fmol dose elicited a rise in LH.
Furthermore, the percentage of GnRH neurons responding to kisspeptin increased
from
50% in pre-pubertal mice and to >90% in adult mice.
Therefore, this study suggests that sensitivity to kisspeptin-52 increases with age
in male mice [ 32 ].
Overall, the sensitivity of the hypothalamo-pituitary-gonadotrophic axis to
exogenous kisspeptin appears to increase after the onset of puberty, with great-
est responses in peri-pubertal periods and during adulthood; these ages may relate
to more mature stages of reproductive development with higher levels of sex hor-
mones, which might infl uence sensitivity to exogenous kisspeptin administration.
~
25% in juveniles to
~
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