Interactions Between Kisspeptins and Neurokinin B - Kisspeptin Signaling in Reproductive Biology - page 329

Fig. 15.5 Percentage of
vaginal opening (V.O.) in
peripubertal female rats
treated chronically with
central injections of vehicle,
the NKB antagonist
SB222200 or the kisspeptin
antagonist p234.
Figure composed based on
the original data presented in
refs. [ 40 , 112 ]
Importantly, despite the documented sensitivity of Tac2 expression to the negative
feedback of sex steroids prepubertally in the mouse [ 70 ], the major regulatory path-
way that drives the stimulation of Tac2 expression prior to puberty onset seems to
be independent and, seemingly, dominates over the rising levels of gonadal steroids
that occur during puberty onset [ 40 , 71 , 114 ].
Additionally, in line with a role for NKB in the timing of puberty, senktide
induces strong secretory responses of LH in juvenile monkeys [ 31 ], prepubertal
male and female rats [ 67 ] and prepubertal ewes [ 115 ], suggesting that the gonado-
tropic axis is responsive to NKB stimulation before puberty onset. On the whole,
these observations, along with recent clinical observations suggesting that the stim-
ulatory action NKB on the gonadotropic axis may be more prominent during early
stages of sexual maturation [ 10 ], are in line with an eventual stimulatory role of
NKB upon Kiss1 expression during pubertal maturation.
Moreover, studies of chronic blockade of NKB signaling using the NK3R antag-
onist, SB222200, to prepubertal female rats induce a slight delay in the timing of
puberty onset (Fig. 15.5 ) [ 40 ]. The effect of this antagonist to block pubertal pro-
gression is, however, not as effective as the chronic administration of a kisspeptin
antagonist, which results in a marked suppression of vaginal opening (Fig. 15.5 )
and gonadal weights—as indirect markers of the rise of circulating sex steroids dur-
ing puberty onset [ 112 ]. In sum, based on the above observations, it is reasonable to
deduce a stimulatory role of NKB in the timing of puberty, an effect which may be
dependent on kisspeptin signaling.
NKB as a Signaling System of the Metabolic Status
Reproduction is an extremely energy-demanding function and, as such, subjected to
regulation by metabolic cues that eventually contribute to the regulation of GnRH
release [ 1 , 116 ]. Mounting data during the last few years suggest that Kiss1 neurons
in the ARC play a critical role conveying metabolic information onto the hypotha-
lamic centers that control the attainment and maintenance of reproductive function.
For instance, models of metabolic stress, such as acute fasting, impinge a signifi cant