Hypothalamic kisspeptin neurons as potential mediators of estradiol negative and positive feedback

Gonadal steroid feedback regulates the brain’s patterned secretion of gonadotropin-releasing hormone (GnRH). Negative feedback, which occurs in males and during the majority of the female cycle, modulates the amplitude and frequency of GnRH pulses. Positive feedback occurs in females when high estradiol induces a surge pattern of GnRH release. These two forms of feedback and their corresponding patterns of GnRH secretion are thought to be mediated by kisspeptin-expressing neurons in two hypothalamic areas: the arcuate nucleus and the anteroventral periventricular area. In this review, we present evidence for this theory and remaining questions to be addressed.