Biology Reference
In-Depth Information
of this sexual dimorphism focused on the well-established organizational effects of
testosterone during the perinatal period. As described in detail elsewhere in this
topic (Chap.
11
), studies in rats using neonatal gonadectomy and/or steroid treat-
ments [
21
,
44
] support the hypothesis that testicular secretion of testosterone during
this period is converted to E
2
, which then produces a permanent decrease in
kisspeptin-expressing cells in the RP3V. This conclusion is also supported by the
effects of genetic manipulations in mice that knocked out the aromatase enzyme
[
141
] or alpha-fetoprotein [
142
]. A similar sexual dimorphism in POA kisspeptin
cell number has been observed in sheep [
31
] and humans [
44
], but the factors
responsible remain unknown.
The effects of estradiol on kisspeptin cell numbers in the RP3V may not be lim-
ited to the perinatal period, since OVX of mice at PND15 reduced
Kiss1
mRNA
expression in the adult RP3V to male levels [
49
]. On the other hand, in hypogonadal
(
hpg
) mice [
50
], the absence of gonadal steroids did not alter the age-related increase
in RP3V kisspeptin-ir cell numbers (although the maximal number was suppressed),
but male
hpg
mice showed a similar increase in RP3V kisspeptin cells that was not
evident in their WT littermates. It should be noted, however, that no age-related
increases in
Kiss1
mRNA (qRT-PCR) were observed in either male or female
hpg
mice [
50
], so there appears to be a mismatch between
Kiss1
mRNA and protein
expression in these mice.
In sheep [
31
] and humans [
44
], there are also signifi cantly more kisspeptin neu-
rons in the ARC of females than males, while in rodents ARC kisspeptin expression
is similar in both sexes [
21
,
135
,
143
]. There is no information on factors responsi-
ble for this sexual dimorphism in humans, but in sheep, organizational effects of
steroids likely play a role because this sex difference is seen in gonadectomized
animals [
130
]. However, prenatal masculinization of females with testosterone
treatment during gestation did not infl uence kisspeptin cell numbers, but it did
decrease the number of NKB-ir and dynorphin-ir cells to levels seen in males [
31
].
Interestingly, the sex differences in ovine ARC kisspeptin expression develop
between 6 and 12 months of ages, as cell numbers in males decline, and are inde-
pendent of gonadal steroids because it is evident in gonadectomized animals [
130
].
In contrast, mice show a sexual dimorphism in ARC kisspeptin neurons that is lost
during development. Specifi cally, OVX of prepubertal females results in a doubling
of kisspeptin cell number, while castration of males prior to puberty has no effect
[
135
], a sex difference not seen in adult mice [
135
].
Conclusions
The mammalian kisspeptin system is remarkably consistent across all species studied
to date, at least that portion of it that has a well-defi ned role in control of GnRH
secretion. Major groups of cell bodies are found in two areas: a large number in the
ARC and smaller set in the POA, which is concentrated in the RP3V of rodents
(Fig.
3.3
). Most neurons in the ARC subpopulation also contain NKB and dynorphin,
Search WWH ::
Custom Search