Uncovering the role of arcuate kisspeptin neurons as a source of the gonadotropin-releasing hormone pulse generator using gene-modified rats

　Strategies for increasing reproductive performance are needed for domestic animals because for example the conception (pregnancy) rate has decreased in dairy cows around the world. Reproductive function is controlled by hormones released by the hypothalamus-pituitary-gonadal axis in mammals, including domestic animals. Of those hormones, tonic (pulsatile) gonadotropin-releasing hormone (GnRH) release is fundamentally important for gonadotropin release and gonadal activity. Therefore, uncovering the mechanism controlling GnRH pulses, that is GnRH pulse generator, is essential to improve reproductive technologies for domestic animals. The present review is focused on the indispensable role of arcuate nucleus (ARC) kisspeptin neurons (also known as KNDy neurons) as the GnRH pulse generator in mammals. First, we give a brief overview of studies on hypothalamic kisspeptin neurons throughout the past two decades. Second, we review studies that have provided direct evidence that ARC kisspeptin neurons serve as the GnRH pulse generator, with a special focus on our gene-modified rat models. Finally, we discuss the mechanism underlying GnRH pulse generation. The knowledge obtained from gene-modified rat models should be clinically important and could be adapted to new tools to improve reproductive performance in livestock by stimulating GnRH/gonadotropin pulses.

総合論文 (Comprehensive paper)