Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System

Highly sophisticated and synchronized interactions of various cells and hormonal signals are required to make organisms competent for reproduction. GnRH neurons act as a common pathway for multiple cues for the onset of puberty and attaining reproductive function. GnRH is not directly receptive to most of the signals required for the GnRH secretion during the various phases of the ovarian cycle. Kisspeptin neurons of the hypothalamus convey these signals required for the synchronized release of the GnRH. The steroid-sensitive anteroventral periventricular nucleus (AVPV) kisspeptin and arcuate nucleus (ARC) KNDy neurons convey steroid feedback during the reproductive cycle necessary for GnRH surge and pulse, respectively. AVPV region kisspeptin neurons also communicate with nNOS synthesizing neurons and suprachiasmatic nucleus (SCN) neurons to coordinate the process of the ovarian cycle. Neurokinin B (NKB) and dynorphin play roles in the GnRH pulse stimulation and inhibition, respectively. The loss of NKB and kisspeptin function results in the development of neuroendocrine disorders such as hypogonadotropic hypogonadism (HH) and infertility. Ca²⁺ signaling is essential for GnRH pulse generation, which is propagated through gap junctions between astrocytes-KNDy and KNDy-KNDy neurons. Impaired functioning of KNDy neurons could develop the characteristics associated with polycystic ovarian syndrome (PCOS) in rodents. Kisspeptin-increased synthesis led to excessive secretion of the LH associated with PCOS. This review provides the latest insights and understanding into the role of the KNDy and AVPV/POA kisspeptin neurons in GnRH secretion and PCOS.