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Fig. 11.2 Sex differences in AVPV Kiss1 cells are organized early in development by perinatal
hormones and are unaffected by the activational effects of adult hormones. Representative photo-
micrographs showing Kiss1 mRNA-expressing cells in the AVPV of adult male, female, and neo-
natally androgenized female rats. All animals were treated in adulthood with E 2 . 3V third ventricle;
Cast castrated; OVX ovariectomized. Modifi ed from Kauffman AS, Gottsch ML, Roa J, Byquist AC,
Crown A, Clifton DK, Hoffman GE, Steiner RA, Tena-Sempere M 2007 Sexual differentiation of
Kiss1 gene expression in the brain of the rat. Endocrinology 148:1774-1783. With permission
from The Endocrine Society
In addition to developmental changes in AVPV/PeN kisspeptin cell number, the
development of kisspeptin fi bers apposing GnRH neurons has been reported to
change over development [ 28 ]. Detectable kisspeptin fi ber appositions to GnRH
neurons were absent in female mice younger than PND 25, but such appositions
were present on PND 25 and further increased in numbers by PND 31 [ 28 ]. The
authors postulated that many of these GnRH-apposing kisspeptin fi bers were
derived from the AVPV/PeN region, though this was not experimentally deter-
mined. However, if this assumption is true, then the appearance and subsequent
pubertal increase in kisspeptin-GnRH appositions may be a function of the known
increase in kisspeptin synthesis in the AVPV/PeN during this age, increasing the
visibility and detection of the fi bers. Alternatively, it is also possible that a physical
increase in the degree of kisspeptin fi ber innervation of GnRH neurons occurs peri-
pubertally, perhaps affecting GnRH activation around puberty onset.
Sexual Differentiation of AVPV/PeN Kiss1 Expression
During Development
A few years ago, it was discovered that Kiss1- expressing neurons in the adult rat
AVPV/PeN are sexually differentiated, with adult females possessing more Kiss1
mRNA (and detectable Kiss1 cells) than males (Fig. 11.2 ) [ 36 ]. Similar observations
have now been reported for Kiss1 mRNA levels in mice [ 40 ] and kisspeptin protein
levels in mice and rats [ 28 , 66 ]. No documented Kiss1 sex differences have yet been
reported in the POA of the ewe or monkey, although a sex difference is observed in
the ARC Kiss1 population of sheep [ 67 ] and is discussed later in further detail.
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