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Conclusions and Considerations
Given the importance of circadian timing in female reproductive functioning and
health, and the key role played by kisspeptin in the circadian network driving ovu-
lation, it is critical that a full understanding of the specifi c mechanisms and neuro-
chemicals pathways driving the timed production and secretion of this neuropeptide
be garnered. The present overview points to the SCN as a central clockwork driving
the coordinated activity of a host of positive and negative regulators of the repro-
ductive axis (Fig.
18.8
). Future studies in which circadian signaling to relevant
nodes downstream of the SCN, as well as circadian timing in these targets loci,
Fig. 18.8
Proposed model of circadian initiation of the preovulatory LH surge in spontaneously
ovulating rodents by major positive and negative regulators of GnRH neuronal activity. Kisspeptin
cells in the AVPV are active at the time of the LH surge. Whereas estrogen-responsive kisspeptin
cells have not been defi nitively shown to project specifi cally to GnRH neurons, the emergence and
sexual dimorphism of kisspeptin cells and fi bers that project to GnRH cell bodies provide compel-
ling evidence for the direct connection between these two neural phenotypes. Connections between
the GnIH and GnRH systems indicate a putative role for GnIH in modulating the negative-feedback
effects of estrogen with SCN communication allowing for removal of negative feedback on the
reproductive axis during the time of the LH surge. Kisspeptin cells in the ARC likely serve to
modify GnRH output at the level of the terminal. See text for additional details. Figure as origi-
nally published in Williams WP 3rd, Kriegsfeld LJ. Circadian control of neuroendocrine circuits
regulating female reproductive function. Front Endocrinol (Lausanne). 2012;3:60. Epub 2012 May
21 doi:
10.3389/fendo.2012.00060
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