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Fig. 19.2
Effect of an intravenous infusion of kisspeptin-10 on LH, FSH, and estradiol secretion
patterns in a representative acyclic anestrous ewe. Administration of kisspeptin led to an immediate
increase in plasma concentrations of LH (
open circles
) and FSH (
closed squares
) for a 4-5 h
period. This was followed by a reduction in the concentrations of the two gonadotropins, but LH
concentrations remained above baseline until a preovulatory surge of the two gonadotropins was
eventually observed. Plasma estradiol concentrations (
black triangles
) were also increased by kiss-
peptin infusion and remained elevated until the occurrence of a gonadotropin surge. Redrawn from
ref. [
95
]
whether kisspeptin treatment reactivates the gonadotropic axis and causes ovulation,
we conducted studies in two breeds of sheep raised in both Northern and Southern
hemispheres. Intravenous infusion of a low dose of kisspeptin-10 was given to
acyclic anoestrus ewes over 48 h [
93
]. This treatment stimulated gonadotropin
secretion, induced LH surges, and caused ovulation in more than 80 % of the anes-
trous animals. Analysis of the hormonal changes induced by this chronic kisspeptin
infusion is illustrated in Fig.
19.2
, indicating a sharp, albeit transient, increase in
serum gonadotropin levels that was maintained for 4-5 h. Thereafter, while FSH
returned to basal levels, LH secretion stayed at follicular phase levels (1-2 ng/mL)
up until a well-synchronized LH surge occurred some 16-22 h later. Thus, in terms
of mechanism, kisspeptin infusion induced a sequence of events similar to a normal
follicular phase, which culminated in the positive feedback of estrogen in these
animals with a quiescent hypothalamo-pituitary axis. This included an initial rapid
stimulation of GnRH secretion, leading to the stimulation of LH secretion to follicu-
lar phase levels, which subsequently activated the ovaries and ultimately led to the
initiation of the positive feedback circuits within the brain and the induction of the
preovulatory LH surge.
An interesting question is why stimulation by kisspeptin can lead to a sustained
level of LH secretion and not be overcome by the negative feedback effect of estro-
gen, which is pronounced in the anestrous season. At least one likely explanation is
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