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In-Depth Information
Introduction
Administration of kisspeptin has been shown to stimulate gonadotropin release in
all non-human mammalian species studied to date. The conserved stimulating effect
of kisspeptin on gonadotropin release in all species studied suggests that kisspeptin
plays a critical and fundamental role in the control of reproduction. However, there
are important differences in the reproductive systems of various mammalian spe-
cies. In addition, although the amino acid structure of kisspeptin-10 is relatively
conserved across species, there may be up to two amino acid differences between
species-specifi c isoforms, which might conceivably result in subtle alterations in
kisspeptin activity.
In this chapter, we summarize the effects of different isoforms of kisspeptin
(kisspeptin-54/kisspeptin-52, kisspeptin-14, kisspeptin-10 of murine or human ori-
gin) on gonadotropin release in various non-human mammals after acute and
chronic administration via various routes (intracerebroventricular [ICV], intrave-
nous bolus [IV bolus], intravenous infusion [IVI], intraperitoneal [IP], subcutane-
ous [SC]). Importantly, the hormone-releasing actions of kisspeptin may be
infl uenced by metabolic status, sex, maturation, and underlying hormonal milieu;
these will also be considered in this chapter. Detailed discussion of the effects of
kisspeptin in humans is present in Chap. 5 .
The Effects of Acute Administration of Kisspeptin
on Gonadotropin Secretion
Kisspeptin has been shown to reliably and rapidly stimulate gonadotropin secretion
when given acutely by a number of different routes. Whilst kisspeptin is considered
to be a neuropeptide, with very low circulating levels in the blood, peripheral admin-
istration has been shown to reliably stimulate gonadotropin release in a number of
species.
Acute Peripheral Administration of Human Kisspeptin-54
or Rat Kisspeptin-52
In 2004, Matsui et al. performed one of the fi rst studies of kisspeptin administra-
tion to any mammalian species. A subcutaneous (SC) bolus of 6.7 nmol of human
kisspeptin-54 (called metastin at the time) in pre-pubertal (25 day old) female
Wistar rats signifi cantly elevated plasma LH levels tenfold from a baseline of
~3 ng/mL and FSH levels sixfold from a baseline of ~10 ng/mL at 2 h post-
injection [ 1 ]. Kisspeptin-54 was also able to elicit ovulation in a large proportion
of follicles, similar to that seen with human chorionic gonadotropin (hCG) [ 1 ].
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