KNDy (kisspeptin/neurokinin B/dynorphin) cells of the arcuate nucleus: a central node in the control of GnRH secretion
M N Lehman
We recently identified a group of neurons in the arcuate nucleus of the mammalian hypothalamus that co-localize three neuropeptides, kisspeptin, neurokinin B and dynorphin, each of which has been shown to play a critical role in the central control of reproduction. Growing evidence suggests that this subpopulation, abbreviated as the KNDy subpopulation, plays a key role in mediating hormonal feedback control of GnRH secretion. KNDy cells are a major target for steroid hormones and have direct projections to GnRH cell bodies and terminals, features that position them well to convey the influence of gonadal steroids to GnRH neurons. In addition, the observation that KNDy neurons form an interconnected network presumably capable of producing a synchronous burst of firing has led to speculation that they may represent an important component of the hypothalamic pulse generator that drives episodic secretion of GnRH. Finally, recent work involving prenatal steroid-treated animal models indicates that alterations in KNDy cell peptides and/or their release may underlie deficits in steroidal feedback control of GnRH secretion and consequent LH excess as seen in clinical reproductive disorders such as polycystic ovarian syndrome (PCOS). Taken together, this evidence suggests a key role for the KNDy subpopulation as a focal point in the control of reproductive function in both health and disease.