Kisspeptin and Seasonality of Reproduction - Kisspeptin Signaling in Reproductive Biology - page 406

In non-operated animals, kisspeptin-ir cell number in the AVPV was reduced in short
days, compared to long days, but cell numbers in the ARC were higher in the long-day
photoperiod, consistent with an earlier observation from this group [ 21 ]. There was no
signifi cant effect of castration of male Siberian hamsters on kisspeptin levels in either
nucleus, in either photoperiod; this is clearly different to the result obtained in Syrian
hamsters [ 57 ]. Testosterone treatment increased kisspeptin-ir cell number in the AVPV
of castrated Siberian hamster males, an effect which was much greater under short
days (in which kisspeptin cell numbers are very low to begin with) [ 58 ]. This result, at
least under short-day photoperiod, is consistent with that seen in the Syrian hamster
(see above), and the result for the AVPV is similar to that seen in the mouse [ 59 ]. On
the other hand, testosterone reduces Kiss1 expression in the ARC of the castrated
mouse [ 59 ], but does not appear to do so in either Syrian or Siberian hamsters, indicat-
ing key species differences.
It has been noted that changes in kisspeptin gene expression or peptide levels in the
ARC could relate to changes in metabolic regulation with season [ 21 ]. Another point
of consideration is that the AVPV is considered to be the site of positive feedback
effects of estrogen on GnRH/LH secretion in mice and rats (and hamsters), whereas
the ARC is the seat of negative feedback control via kisspeptin cells [ 33 ]. Accordingly,
it is interesting that there are seasonal changes in the AVPV of the hamster in both
sexes. These data are complex and further studies are required before the seasonal
control of reproduction in the two different hamster species is fully understood.

Kisspeptin and Seasonal Reproduction

As indicated in the Introduction, an increase in the negative feedback effect of estro-
gen on GnRH/LH secretion is a fundamental cause of seasonal anestrus in the ewe
[ 9 , 11 ]. In normal Soay ewes, expression of Kiss1 in the ARC fell when the animals
were transitioned from a photoperiod of 8 h light and 16 h dark to longer day lengths
[ 60 ], consistent with the short-day breeding pattern of this species. Other studies
have shown that the number of Kiss1 -expressing and kisspeptin-immunoreactive
(-ir) cells in the ARC is greater in the brains of ovariectomized ewes at the time they
would normally (if gonad int.ct) be breeding. This effect was seen irrespective of
whether the animals were treated with long-term estrogen implants [ 30 , 49 ], but the
inhibitory effects of long-term estrogen treatment on Kiss1 mRNA and kisspeptin
expression in the ARC (indicative of negative feedback) are greater during the
nonbreeding season [ 30 ]. These data suggest the seasonal change in sensitivity to
estrogen, which is a major mechanism for seasonal reproduction (see above), is
affected, at least in part, by changing responsiveness of the kisspeptin cells to estro-
gen. The subcellular mechanisms that underlie this fundamental change in respon-
siveness to estrogen have not been elucidated, and it is not known if the level of ER α

expression in ARC kisspeptin cells changes with season. This seasonal effect on
Kiss1 was seen in the ARC, but not the POA, supporting the notion that the negative
feedback effect is promulgated by this subset of kisspeptin cells. In another study [ 61 ],