The Effects of Kisspeptin on Gonadotropin Release in Non-human Mammals - Kisspeptin Signaling in Reproductive Biology - page 61

Chapter 4
The Effects of Kisspeptin on Gonadotropin
Release in Non-human Mammals
Ali Abbara , Risheka Ratnasabapathy , Channa N. Jayasena ,
and Waljit S. Dhillo
Abstract The Kiss1 gene encodes a 145-amino acid pre-peptide, kisspeptin, which
is cleaved into smaller peptides of 54, 14, 13, and 10 amino acids. This chapter
reviews in detail the effects of kisspeptin on gonadotropin secretion in non-human
mammals. Studies of kisspeptin's effects have included both acute and chronic
administration regimens via a number of administration routes. Acute kisspeptin
stimulates gonadotropin secretion in a wide range of species of non-human mam-
mals, including rats, mice, hamsters, sheep, pigs, goats, cows, horses, and monkeys.
In general, the stimulatory effect of kisspeptin treatment is more pronounced for LH
than FSH secretion. Kisspeptin is thought to exert its stimulatory effects on LH and
FSH release via stimulation of GnRH release from the hypothalamus, since pre-
administration of a GnRH antagonist prevents kisspeptin's stimulation of gonado-
tropin secretion. Although the kisspeptin receptor is also expressed on anterior
pituitary cells of some species, and incubation of anterior pituitary cells with high
concentrations of kisspeptin can stimulate in vitro LH release, the contribution of
direct effects of kisspeptin on the pituitary is thought to be negligible in vivo.
Continuous kisspeptin administration results in reduced sensitivity to the effects of
kisspeptin, in some species. This desensitization is thought to occur at the level of
the kisspeptin receptor, since the response of the pituitary gland to exogenous GnRH
is maintained. Overall, the fi ndings discussed in this chapter are invaluable to the
understanding of the reproductive role of kisspeptin and the potential therapeutic
uses of kisspeptin for the treatment of fertility disorders.
A. Abbara ￿ R. Ratnasabapathy ￿ C.N. Jayasena ￿ W. S. Dhillo ( * )
Division of Diabetes, Endocrinology and Metabolism, Department of Investigative
Medicine, Imperial College London, London , W12 ONN , UK
e-mail: [e-mail]; [e-mail]