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its action on
Kiss1
neurons but, also, serves as a conveyor of additional regulatory
factors, e.g., developmental and metabolic, to
Kiss1
neurons, thus contributing to
the exquisite regulation of kisspeptin release.
Many aspects of the physiology of the NKB/NK3R system in the context of
reproduction remain to be fully characterized. For instance, a vivid debate is cur-
rently ongoing in the fi eld regarding the putative target/s of NKB, with evidence on
both
Kiss1
and GnRH neurons that may only refl ect species differences or, perhaps,
residual levels of redundancy that, under constitutive absence of one or another,
may lead to potential compensation. Additionally, important aspects regarding the
sexual differentiation of the response of gonadotropins to NKB (or senktide), as
recently observed in the rat, constitute a mystery that demands to be resolved.
Indeed, reconciliation of the results in male mice and rats, and a detailed compari-
son between both sexes, to determine which one better resembles the human pheno-
type would clearly help the scientifi c community to establish a working model with
translational potential to humans. Overall, elucidating how the brain triggers the
neuroendocrine events that lead to the attainment and maintenance of reproductive
function will provide the intellectual platform for understanding certain disorders of
reproduction, including delayed or precocious puberty—and perhaps guide us
toward improved therapies for their treatment.
Acknowledgments
This research was supported by the Marie Curie Outgoing International
Fellowship within the seventh Framework Programme of the European Union. The author is grate-
ful to Drs. Amy Oakley and Leonor Pinilla for their constructive comments on the manuscript and
Drs. Manuel Tena-Sempere, Don Clifton, and Robert Steiner for their contribution to some of the
studies highlighted in this chapter.
Confl ict of interest: The author reports no confl icts of interest.
Disclosure: The author has nothing to disclose.
References
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