Studies on the Character of Hypothalamic GnRH Neurons and Kisspeptin Neurons Using Hypothalamic Cell Models

The hypothalamic-pituitary-gonadal (HPG) axis controls the hormonal network responsible for reproductive functions. In the past, hypothalamic gonadotropin-releasing hormone (GnRH) neurons have been positioned at the highest level in the HPG axis. After the discovery of the indispensable roles of hypothalamic kisspeptin in GnRH neurons, our ­understanding­of­the­neuroendocrine­regulation­of­the­HPG­axis­was­reconfirmed,­and­it­is­ now recognized that hypothalamic kisspeptin neurons are positioned at the summit of the HPG axis. Accumulating evidence shows that kisspeptin neurons are responsible for the onset of puberty and sex steroid feedback mechanisms by modulating the activity of GnRH neurons.­Furthermore,­the­identification­of­kisspeptin­in­the­hypophyseal­portal­circulation­ suggests that this peptide has some direct roles in the pituitary gland. The detailed mechanisms underlying the regulation of GnRH by kisspeptin and the regulatory control of kisspeptin neurons are still largely unknown because of the limitations of the experimental models. The establishment of GnRH-expressing and kisspeptin-expressing cell models has enabled us to examine the character of these neuronal cells. In this chapter, we describe our in vivo studies examining the character of GnRH neurons and kisspeptin neurons in the hypothalamus using hypothalamic GnRHand/or kisspeptin-expressing cell models.