Abstract:
Kisspeptins are products of the KiSS-1 gene, which bind to a G
protein-coupled receptor known as GPR54. Mutations or targeted disruptions
in the GPR54 gene cause hypogonadotropic hypogonadism in humans and mice,
suggesting that kisspeptin signaling may be important for the regulation
of gonadotropin secretion. To examine the effects of kisspeptin-54
(metastin) and kisspeptin-10 (the biologically active C-terminal
decapeptide) on gonadotropin secretion in the mouse, we administered the
kisspeptins directly into the lateral cerebral ventricle of the brain and
demonstrated that both peptides stimulate LH secretion. Further
characterization of kisspeptin-54 demonstrated that it stimulated both LH
and FSH secretion, at doses as low as 1 fmol; moreover, this effect was
shown to be blocked by pretreatment with acyline, a potent GnRH
antagonist. To learn more about the functional anatomy of kisspeptins, we
mapped the distribution of KiSS-1 mRNA in the hypothalamus. We observed
that KiSS-1 mRNA is expressed in areas of the hypothalamus implicated in
the neuroendocrine regulation of gonadotropin secretion, including the
anteroventral periventricular nucleus, the periventricular nucleus, and
the arcuate nucleus. We conclude that kisspeptin-GPR54 signaling may be
part of the hypothalamic circuitry that governs the hypothalamic secretion
of GnRH.
