Kisspeptin and Puberty in Mammals - Kisspeptin Signaling in Reproductive Biology - page 250

Developmental Changes in the Kisspeptin Neuronal System
Kisspeptin neurons in the adult hypothalamus are typically found in both the medial
basal hypothalamus (MBH) and the preoptic area (POA) (see Chap. 3 ) . In the MBH,
kisspeptin neurons are localized in the arcuate nucleus (ARC, synonymous with
infundibular nucleus in humans), and in the POA, these cells are found in the antero-
ventral periventricular nucleus (AVPV) in rodents and in similar areas in other spe-
cies. Kisspeptin neurons in the ARC are considered to be an important component
of the hypothalamic control of tonic gonadotropin secretion in all species, while
kisspeptin neurons in the AVPV of rodents are critical for surge secretion of GnRH
and LH, and therefore for ovulation [ 31 ].
Overall expression of Kiss1 mRNA in the hypothalamus (AVPV and ARC
combined) is signifi cantly elevated around the time of puberty in both male and
female rats [ 32 ]. In the ARC, Kiss1 mRNA levels in female rats at postnatal day
26 (P26), i.e., 3-4 days before vaginal opening, are over fourfold higher than
those at P21 [ 33 ], although changes in the number of Kiss1 -expressing neurons
from P3 to adulthood are unremarkable [ 34 ]. In male rats, Kiss1 mRNA levels in
the ARC at P45 are signifi cantly higher than those at P15 [ 35 ], and the number of
Kiss1 neurons increases progressively throughout postnatal development [ 34 ]. In
male mice, however, a developmental increase in Kiss1 mRNA levels in the ARC
has not been observed [ 36 - 38 ]. Moreover, whereas ovariectomy in female mice
at P14 dramatically increases expression of ARC Kiss1 mRNA by P16-P18, i.e.,
well before puberty onset, castration at P14 in male mice does not result in
increased ARC Kiss1 mRNA or LH release at P18 [ 39 ]. However, expression of
both the ARC Kiss1 mRNA and secretion of the gonadotropin were elevated at
P45 in male mice castrated at P14 [ 39 ]. Interestingly, in both male and female
mice, Kiss1 expression is detected in the ARC on P1, and at least in females, kiss-
peptin receptor signaling appears to be driving gonadotropin release at this early
stage of development [ 40 ]. The absence of a post-castration LH response in pre-
pubertal male mice has been previously reported [ 41 ], and differs from the situa-
tion in rats and guinea pigs where prepubertal orchidectomy elicits a robust
increase in LH secretion [ 29 , 30 , 42 ]. In an alternative paradigm to eliminate the
confounding effect of testicular steroid feedback on the development of Kiss1
expression in mice, Gill et al. [ 38 ] studied the hpg mouse, a GnRH defi cient
hypogonadal animal, and found that ARC Kiss1 expression increases dramati-
cally between P10 and P30 (as it also did in the hpg female). Clearly, the devel-
opmental pattern in Kiss1 expression in the ARC of the male mouse requires
further study.
In the rhesus monkey, pubertal increases in KISS1 mRNA in the MBH (presum-
ably in the ARC) in ovarian intact female and agonadal male monkeys have been
observed [ 43 ]. Although a gonadal steroid-independent pubertal increase in KISS1
mRNA expression in female monkeys has not been examined, an ovarian steroid-
independent increase in kisspeptin release in the region of the ARC-median emi-
nence (ARC-ME) has been observed (see next section).