Kisspeptin and Seasonality of Reproduction - Kisspeptin Signaling in Reproductive Biology - page 413

did so [ 100 ]. These authors suggested that failure of continuous delivery could have
been partly due to degradation of kisspeptin in the mini-pumps, an inappropriate
dose, and/or downregulation of the kisspeptin receptors after chronic treatment.
Another point of difference between the two studies was that Ansel et al. [ 100 ] used
kisspeptin-54, whereas Greives et al. [ 58 ] used kisspeptin-10. Nevertheless, there is
little difference in the potency of the two forms, even though kisspeptin-54 shows a
slightly delayed effect [ 101 ].
The above fi ndings raise the question of why does continuous peripheral kiss-
peptin treatment of sexually quiescent Syrian hamsters fail to activate the gonads,
whereas continuous treatment of ewes does so Furthermore, one might ask why
intermittent kisspeptin treatment of anestrous ewes was not effective, whereas con-
stant infusion was so [ 93 ]. The answers are not yet known, but may be because the
acute response in the anestrous ewe is a rise in LH secretion, suffi cient to cause a
rise in plasma estrogen levels, and it is the latter that then leads to a positive feed-
back response and an ovulatory LH surge. In this respect, nuances in the response
to kisspeptin, in relation to species and the type of response being sought (male vs.
female), need careful consideration.
Concluding Remarks
Kisspeptin cells appear to be integrally involved in the transitions into and out of the
breeding seasons. Generally, there is an increase in the activity of ARC kisspeptin
cells in the breeding season and a reduction in the nonbreeding season. Because
these cells are estrogen responsive, they are able to transduce the enhanced negative
feedback effect of estrogen that suppresses GnRH secretion in the nonbreeding
season. Consistent with the fi ndings in terms of cellular function, some kisspeptin
treatments allow maintenance of reproductive function in hamsters housed in short-
day (inhibitory) photoperiod and cause ovulation in anestrous ewes.
Data from hamsters and sheep strongly suggest that the seasonal changes in
kisspeptin function are due to photoperiod, and more specifi cally, the pattern of
melatonin secretion, but a means by which melatonin acts to cause these changes is
a fundamental issue that requires some resolution before we can fully understand
mechanisms of seasonal breeding.
In sheep at least, there appears to be a reciprocal change in the function of GnIH
cells and kisspeptin cells that are complementary, such that reduced activity of kiss-
peptin and increased function of GnIH both suppress reproductive function in the
anestrous season. This does not seem to be the case in Syrian or Siberian hamsters,
where GnIH expression is surprisingly decreased during inhibitory (short day) pho-
toperiod. Even though kisspeptin cells play a pivotal role in the reproductive
response to photoperiod, a greater level of understanding of the afferents to kiss-
peptin cells is required before we can determine how seasonality of reproduction is
actually controlled by melatonin.