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action; it is therefore expected that a centrally administered dose of kisspeptin
would be more effective in stimulating gonadotropin secretion when compared with
peripheral administration.
In one study in rats, an IV bolus dose of 7.5 nmol of kisspeptin-10 increased
plasma LH levels to a similar extent, although for a shorter duration, when com-
pared with ICV administration of the same dose [
5
]. Furthermore, an IV bolus of
1,000 pmol/kg of human kisspeptin-10 increased LH secretion to a similar degree
when compared with ICV administration of a much smaller dose (200 pmol/kg) in
ovariectomized adult ewes [
50
]. A comparison was also made between 150 nmol of
murine kisspeptin-10 administered as a SC bolus or as a 6 h constant IV infusion in
ewes. After SC bolus administration, plasma LH secretion was increased 3.6-fold
for 90 min post-injection (a smaller rise in plasma FSH levels was also noted). On
contrast, after an IV infusion, plasma LH levels rose more gradually, with a peak
response 2-4 h later. Interestingly, there was a progressive decline in plasma LH
levels after this peak, despite continuing IV infusion, which may suggest gradual
desensitization to the ongoing presence of kisspeptin [
25
]. Hence, an IV infusion
was able to stimulate LH levels to a greater peak level when compared with SC
administration; however, peak levels following IV infusion occur later when com-
pared with SC bolus administration. The effects of IM and IV injection of human
kisspeptin-10 were also compared in Japanese pre-pubertal calves (5-6 months of
age). A 3.85 nmol/kg dose of human kisspeptin-10 stimulated a ~10-fold increase
in plasma LH following IV injection. By comparison, only a threefold increase in
plasma LH was observed following IM administration [
51
].
Collectively, the above results indicate that, although kisspeptin is likely to
exert its action centrally, IV bolus administration is associated with a rapid and
powerful short-term stimulation of gonadotropin secretion. Moreover, IM or SC
kisspeptin administration may be associated with more sustained absorption of
kisspeptin; this may cause a lower peak but longer duration of gonadotropin stimu-
lation when compared with IV bolus administration. IV infusion of kisspeptin
results in less rapid yet more sustained stimulation when compared with bolus SC
administration, but with greater risk of eventual desensitization to the effects of
kisspeptin.
Effect of Nutritional State on Gonadotrophic
Response to Kisspeptin
Fertility is reduced during undernutrition. Hypothalamic kisspeptin neurons have
been proposed as an intermediary in the communication between leptin and GnRH
neurons (see Chap.
17
). In adult male Rhesus monkeys, 50
g (38.4 nmol) of human
kisspeptin-10 was administered IV in a fed state or following a 48 h fast. Following
kisspeptin administration, peak testosterone secretion was signifi cantly reduced and
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