Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment
Stéphanie Constantin, Daniel Reynolds, Andrew Oh, Katherine Pizano, Susan Wray
Abstract
Significance Hypothalamic neural networks control hormone secretion to maintain body function. For gonadotropin-releasing hormone (GnRH) neurons, critical to fertility, release must be pulsatile. While it is clear that kisspeptin neurons trigger GnRH activity and pulses, how GnRH neurons return to baseline activity before the next stimulation is unknown. Here, we show 1) that the long-lasting response of GnRH neurons to kisspeptin depends on the degradation of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and its slow resynthesis keeping canonical transient receptor potential channels opened and 2) a mechanism whereby nitric oxide facilitates PIP 2 resynthesis and GnRH neuron recovery from kisspeptin activation. Defining the overlap in kisspeptin and nitric oxide signaling pathways may provide an avenue for fertility treatment.