Kisspeptin and Puberty in Mammals - Kisspeptin Signaling in Reproductive Biology - page 248

IPI Inter-pulse interval

KISS1 Kisspeptin gene (primates)

Kiss1 Kisspeptin gene (non-primates)

KISS1R Kisspeptin-1 receptor (primates)

Kiss1r Kisspeptin-1 receptor (non-primates)

KP Kisspeptin

MBH Medial basal hypothalamus

ME Median eminence

S-ME Stalk-median eminence

NPY Neuropeptide Y

POA Preoptic area

Introduction

The discovery, nearly a decade ago, that the G-protein coupled receptor, KISS1R
(aka GPR54), and its ligand, kisspeptin, encoded by the genes KISS1R and KISS1 ,
respectively, play a major role in regulating the hypothalamic-pituitary-gonadal axis
has provided a new perspective on the mystery of puberty. As discussed in Chap. 9 ,

Seminara et al. [ 1 ] and de Roux et al. [ 2 ] fi rst described amino acid mutations of
KISS1R in human patients with a delay in puberty onset or an abnormality in puber-
tal development. Subsequently, several reports also described mutations at different
sites of the KISS1R gene in patients with either an absence of or a delay in puberty
[ 3 - 7 ] or with precocious puberty [ 8 ]. Moreover, it has been reported that a geneti-
cally targeted deletion of either Kiss1r or Kiss1 in mice results in hypogonadotropic
hypogonadism, including delayed pubertal maturation [ 1 , 9 - 11 ]. Most recently,
impairment of pubertal progression in a human family with a mutation of KISS1
was described [ 12 ].
Despite a plethora of reports on kisspeptin and its receptor in relation to puberty
over the last 10 years, a critical evaluation of the role of kisspeptin signaling in the
timing of puberty onset is missing. In this review, we will discuss (1) postnatal
development of kisspeptin neurons and the kisspeptin receptor in relation to parallel
changes in activity of the GnRH neuronal network, an increase in which is obliga-
tory for puberty onset, (2) recent fi ndings on development of kisspeptin signaling in
the rhesus monkey, and (3) our conceptualization of the role played by kisspeptin
signaling in the mechanism that controls the onset and progression of puberty.

Developmental Changes in GnRH Release

An increase in GnRH release from the hypothalamus triggers puberty. Pulsatile
infusion of GnRH induces precocious puberty in sexually immature female and
male monkeys and female guinea pigs [ 13 - 15 ] and increased pubertal release of