Kisspeptin Antagonists - Kisspeptin Signaling in Reproductive Biology - page 155

Chapter 8
Kisspeptin Antagonists
Antonia Kathryn Roseweir and Robert P. Millar
Abstract Kisspeptin is now known to be an important regulator of the hypothalamic-
pituitary-gonadal axis and is the target of a range of regulators, such as steroid
hormone feedback, nutritional and metabolic regulation. Kisspeptin binds to its
cognate receptor, KISS1R (also called GPR54), on GnRH neurons and stimulates
their activity, which in turn provides an obligatory signal for GnRH secretion—thus
gating down-stream events supporting reproduction. The development of peripherally
active kisspeptin antagonists could offer a unique therapeutic agent for treating
hormone-dependent disorders of reproduction, including precocious puberty, endo-
metriosis, and metastatic prostate cancer. The following chapter discusses the advances
made in the search for both peptide and small molecule kisspeptin antagonists and their
use in delineating the role of kisspeptin within the reproductive system. To date,
four peptide antagonists and one small molecule antagonist have been designed.
Introduction
The HPG axis regulates reproduction via the modulation of GnRH production as a
consequence of multiple pathways acting within the hypothalamus [ 1 - 3 ]. Kisspeptin
(KP), acting via its cognate receptor, KISS1R (also called GPR54), has been shown
A. K. Roseweir
Institute of Pharmacy and Biomedical Sciences, University of Strathclyde,
Glasgow , Scotland , UK
Institute of Cancer Sciences, School of Medicine, Veterinary
Medicine and Life Sciences, University of Glasgow, Glasgow, Scotland, UK
e-mail: [e-mail]
R. P. Millar, M.Sc., Ph.D., M.R.C.Path., F.R.C.P.Path. ( * )
Department Zoology and Entomology, University of Pretoria,
Private Bag X 20, Hatfi eld 0028 , South Africa
e-mail: [e-mail]