Figure 5. Schematic representation of the neuronal pathways known to stimulate GnRH/LH release in the female mouse.

The first pathway involves Kiss1 neurons located in the arcuate nucleus (ARC), which also express neurokinin B and dynorphin (thus, often referred to as KNDy neurons). These cells have been mainly implicated in the regulation of GnRH/LH pulsatile secretion in males and females. The second GnRH/LH stimulating mechanism, originates from Kiss1 cells located in the anteroventral periventricular/periventricular preoptic nucleus (AVPV/PeN) and is mainly implicated in the generation of the GnRH/LH surge, which leads to ovulation, and is specific to females. The third and fourth stimulating mechanisms are described in this study and originate from the posterodorsal medial amygdala (MePD). Thus, the third mechanism known to stimulate GnRH/LH release involves Kiss1 neurons and the fourth NK3R expressing neurons of unknown phenotype. The latter are activated only in the presence of estradiol in a mechanism that is female specific. The precise neuronal pathway linking these MePD cells with the stimulation of GnRH/LH release, as well as the physiological relevance of this stimulation, remains to be elucidated. ARC: Arcuate Nucleus, AVPV/PeN: anteroventral periventricular/periventricular preoptic nucleus, MePD: posterodorsal medial amygdala, NK3R: neurokinin receptor 3, κOR: κ opioid receptor, Kiss1r: kiss1 receptor, opt: optic tract.