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normal activation and function of the gonadotropic axis (
Tena-Sempere,
Pinilla, Gonzalez, &Aguilar, 2000
), persistently suppressed the hypothalamic
expression of
Kiss1
gene at the expected time of puberty and adulthood
in the rat
(
Navarro, Fernandez-Fernandez, et
al., 2004; Navarro,
Sanchez-Garrido, et al., 2009
).
Additional evidence for the influence of early sex steroid input for proper
sexual organization of the hypothalamic Kiss1 system came from the studies
involving neonatal gonadectomy (GNX) of male rats, a procedure that
results in the elimination of androgen actions during the critical period of
brain sex differentiation. This manipulation induced the
feminization
of
Kiss1
/kisspeptin expression at the RP3V, namely, males undergoing neona-
tal GNX displayed higher expression than control male rats in adulthood
(
Homma et al., 2009
). Furthermore, neonatal GNX also caused the acqui-
sition of positive feedback and surge-like LH responses to ovulatory doses of
estradiol (
Homma et al., 2009
), which is a characteristic female trait. These
findings would suggest that feminization of the RP3V Kiss1 population is
merely a
default
pathway. However, more recent data from the hypogonadal
hpg
mouse, which is severely deficient in GnRH secretion and, hence, has
very low sex steroids levels, evidenced that
hpg
female mice have lower
numbers of kisspeptin neurons in the RP3V than controls and do not show
the normal stimulatory response to estrogen at this nucleus, thus suggesting
that some degree of estrogenic input is needed for the complete functional
differentiation of RP3V population of Kiss1 neurons also in the female (
Gill
et al., 2010
).
While compelling evidence supports that the RP3V population of
Kiss1 neurons is sexually dimorphic, a feature that is likely to contribute
to the differential timing of puberty between sexes (
Clarkson et al., 2010;
Kauffman, Navarro, Kim, Clifton, & Steiner, 2009
), it remains debatable
whether the same applies to the ARC population of Kiss1 neurons. Thus,
initial studies, assessing
Kiss1
mRNA expression, suggested that the ARC
population of Kiss1 neurons is not sexually dimorphic in the rat
(
Kauffman et al., 2007
). However, more recent analyses have illustrated that,
as is the case in the RP3V, Kiss1 neurons in the ARC are likely more numer-
ous in the female, as documented recently by immunohistochemical and/or
in situ
hybridization studies in rodents, sheep, and primates (
Cheng, Coolen,
Padmanabhan, Goodman, & Lehman, 2010; Hrabovszky et al., 2010;
Takumi, Iijima, & Ozawa, 2011
). Moreover,
Kiss1
mRNA levels in the
ARC seem to be higher in female rats already during the neonatal period,
as reported recently (
Cao & Patisaul, 2011
). Interestingly, studies in the
