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Fig. 14.3 Dual labeling of kisspeptin and NKB in the E2-treated OVX goat. Photomicrographs of
sections of the POA ( a - c ) or ME ( d - f ) immunostained for kisspeptin ( a and d ) and NKB ( b and e ).
( c , f ) are computer-aided merged images of ( a ) and ( b ), or ( d ) and ( e ), respectively. The arrows in
( a ) and ( c ) indicate cell bodies containing exclusively kisspeptin immunoreactivity. The green , red ,
and yellow arrowheads show kisspeptin, NKB, and kisspeptin/NKB positive fi bers. Note that a
majority of kisspeptin positive fi bers contain NKB immunoreactivity ( f ) at the ME. MEe the external
layer of the ME; pt pars tuberalis. Scale bar: 50
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Roles of NKB/NK3R, Dyn/KOR, and Kisspeptin/Kiss1r
Signaling Pathways in the GnRH Pulse Generation
NKB/NK3R Signaling
The involvement of NKB in the control of GnRH/LH secretion was initially
proposed based on morphological changes in NKB neurons in the ARC (the
infundibular nucleus in primates) of postmenopausal women and experimental
animals [ 67 , 83 ]. The proposition is strongly supported by the fi nding that muta-
tions in either Tac3 or Tacr3 (which encode NKB and NK3R, respectively) cause
severe gonadotropin defi ciency in humans [ 89 , 90 ] and that Tacr3 null mice
show reduced gonadal activities, although they are not completely infertile [ 91 ].
Those studies predicted the stimulatory action of NKB on GnRH/LH secretion,
but initial reports provided a controversial view indicating that senktide (a selec-
tive NK3R agonist) decreased LH secretion in rats [ 92 ] and mice [ 57 ].
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