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[ 91 ]. The physiological role of Kiss1r in the pituitary remains unclear because
effects of kisspeptin on LH secretion from pituitary cells in vitro are not consis-
tently observed [ 95 , 96 ], and when kisspeptin stimulates LH secretion, its effects are
generally modest compared to those of GnRH [ 91 , 93 , 97 , 98 ]. Moreover, although
kisspeptin was detected in hypophysial portal blood, the low concentrations and
lack of correlation with LH concentrations in jugular samples led the authors to
conclude that hypothalamic release of kisspeptin played no physiological role in
regulation of LH in the ewe [ 91 ]. It should be noted that kisspeptin mRNA and pro-
tein have been observed in the anterior pituitary in species ranging from rats [ 94 ] to
primates [ 99 ], so Kiss1r could play a paracrine role in this tissue.
Cellular Expression
Not surprisingly, most studies that have examined cellular Kiss1r localization have
focused on GnRH neurons. Studies using dual ISH (Table 3.5 ) consistently report
that a high percentage of GnRH cells from the POA contain Kiss1r ; in female sheep
this percentage ranged from 78 to 90% [ 35 , 86 , 87 ], in male rats it averaged 77%
[ 20 ], and in adult male [ 13 ] and female [ 100 ] mice greater than 85% co-localization
was observed. A slightly lower percentage ranging from 55% [ 88 ] to 68% [ 78 ] was
observed in male mice using Xgal as a marker for Kiss1r , and the lowest percentage
of co-localization (3/8 cells) was obtained using single cell RT-PCR [ 101 ]. The rela-
tive low level of expression in the latter study may have been due to the use of fetal
cells [ 78 ]. A high degree of expression of Kiss1r in GnRH neurons is also supported
by the 90% of murine GnRH neurons that respond to kisspeptin in slice preparations
[ 13 ], since this effect is independent of other neural input [ 13 , 102 ].
Only two other cell types have been examined for possible expression of Kiss1r .
Based on dual ISH techniques, kisspeptin neurons in the POA and ARC of the sheep
do not contain Kiss1r [ 86 ]. On the other hand, ARC POMC neurons in mice most
likely do contain Kiss1r because these cells consistently respond to direct applica-
tion of kisspeptin in slice preparation, even when pharmacologically isolated from
other neural inputs [ 85 ]. It will be important, however, to confi rm this conclusion
using anatomical approaches.
Matches/Mismatches of Kiss1r and Kisspeptin Fibers
Under most circumstances, Kiss1r receptors are presumably only physiologically
important if they are located in neurons innervated by kisspeptin-containing
synapses. Thus, the occurrence of receptor-ligand matches and mismatches in the
kisspeptin system can provide potentially useful information about physiological
signifi cance. On the other hand, the presence of kisspeptin terminals in areas devoid
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