%0 Journal Article
%T Effects of the Hormone Kisspeptin on Reproductive Hormone Release in Humans
%A Joanne L. Calley
%A Waljit S. Dhillo
%J Advances in Biology
%D 2014
%R 10.1155/2014/512650
%X The kisspeptins are a family of neuropeptides which act as upstream stimulators of gonadotrophin releasing hormone (GnRH) neurons. Kisspeptin signalling is prerequisite to establishing the normal human reproductive phenotype; loss of function mutations in the KISS1 or KISS1R gene produces normosmic hypogonadotrophic hypogonadism in humans and mice, whilst increased activation of KISS1R causes precocious puberty. Administration of exogenous kisspeptin to human subjects stimulates an acute gonadotrophin rise. Serum kisspeptin levels also markedly increase during pregnancy. The identification of kisspeptin has been one of the biggest discoveries in the field of reproductive endocrinology, since the isolation and sequencing of GnRH in 1977, and has generated a novel research avenue which has received much attention over the past decade. This research has delineated many properties of the KISS1-KISS1R system, but there is still further work to do. Understanding kisspeptin¡¯s role throughout our reproductive lifetime should help us better understand¡ªand therefore treat¡ªdisorders of reproductive function. Promisingly, the current data supports the potential to develop kisspeptin based therapies. As an outlook article this paper focusses predominantly on our groups recent investigations into the effects of kisspeptin administration to humans and the potential therapeutic role of kisspeptin. 1. Introduction 1.1. Molecular Structure, Function, and Neuroanatomy of Kisspeptin Kisspeptins are coded for by the KISS1 gene and act via binding with the G-protein coupled receptor 54 (GPR54) also known as the KISS1 receptor (KISS1R). The initial protein product of the KISS1 gene is a 145-amino-acid peptide, a member of the arginine phenylalanine (RF) amide group. It is cleaved into shorter, biologically active peptides known as kisspeptin-54, kisspeptin-14, kisspeptin-13, and kisspeptin-10, where each number corresponds to the number of amino acids and with kisspeptin-10 representing the common C-terminal decapeptide sequence shared by all [1]. Kisspeptin expression has been identified in multiple tissues, including pancreas, adipose tissue, gonads, and placenta [1¨C3]; however, its main functional role is mediated by its expression within the central nervous system. Kisspeptin is produced by neurones in the infundibular (arcuate) nucleus of the hypothalamus. These neurons have been shown to have direct afferent connections onto GnRH neurons of the mediobasal hypothalamus in humans, and kisspeptin activity has been shown to induce upregulation of KISS1R within these GnRH
%U http://www.hindawi.com/journals/ab/2014/512650/