Figure 2.

Pathways for leptin’s permissive actions in the hypothalamus. Stimulation by leptin is mediated by neurons in the ventral premammillary nucleus (PMV), which send connections to kisspeptin neurons in the anteroventral periventricular and caudal arcuate nuclei and stimulate Kiss1 expression by glutamate, PACAP or nitric oxide. Also, leptin normally inhibits the orexigenic AgRP–NPY–GABAergic neurons in the arcuate. When leptin signals are reduced (by food deprivation, for example), these neurons signal kisspeptin neurons in the AVPV and caudal arcuate, inhibiting the expression of Kiss1 by AgRP or GABA. These actions ultimately stimulate or inhibit GnRH neurons and modulate pulsatile activity to effect gonadotropin secretion and the LH surge.