**3. Kisspeptin in ovulation**

At mid-cycle, estrogen secreted by the preovulatory follicle eventually triggers GnRH neurons to transition from pulsatile GnRH secretion to sustained secretion. The mechanism by which estrogen transforms from a negative to positive feedback signal on the hypothalamus still remains unclear. Estrogen binds to the ERα receptor on kisspeptin neurons in the arcuate nucleus, inhibiting kisspeptin secretion and subsequent GnRH secretion [15]. In the anteroventral periventricular nucleus, estrogen binds kisspeptin ERα receptors and exerts positive feedback, which ultimately initiates the LH surge associated with ovulation.

The sustained secretion of high concentrations of GnRH (GnRH surge) occurs for over 24 hours and triggers the pituitary gland to secrete high levels of LH (LH surge) [19]. The LH surge is what ultimately triggers ovulation [7]. The LH surge is also the target of at-home ovulation predictor kits [14]. This cascade of hormone surges is thought to be primarily regulated by kisspeptin; in fact, kisspeptin is the most potent activator of GnRH neurons discovered to date [5]. It is suspected that rising estrogen levels during the follicular phase stimulate kisspeptin neurons, which then activate GnRH neurons to initiate the GnRH surge [7]. In contrast,

#### *The Role of Kisspeptin in the Ovarian Cycle, Pregnancy, and Fertility DOI: http://dx.doi.org/10.5772/intechopen.98446*

administration of a monoclonal antibody that blocks kisspeptin has been shown to prevent ovulation in rat models [20].

It is postulated that kisspeptin could be useful as a biomarker of the periovulatory/ovulatory phase [14]. This would be clinically useful because kisspeptin surges prior to LH and therefore could predict the time of ovulation before it happens (rather than as it happens). The target of most ovulation prediction kits is LH, which surges at the time of ovulation. According to Zhai et al., the probability of ovulation is increased when kisspeptin surges on the 11th day and LH surges on the 14th day [14]. In comparison, a study by Goto et al. showed that administration of a kisspeptin antagonist resulted in shrinkage of ovarian follicles and delayed ovulation [21].
