Kisspeptin, Neurokinin B, and Dynorphin A Orchestrate GnRH Pulse Generator Activity in Livestock Reproduction

Normal reproductive function in mammals critically depends on the pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This rhythmic release drives pulsatile gonadotropin secretion from the anterior pituitary, which in turn regulates gonadal activity. Classic studies have shown that continuous GnRH infusion suppresses pituitary responsiveness, underscoring the necessity of pulsatile release. The neural mechanism governing this rhythm is the GnRH pulse generator, a central regulator of the hypothalamus-pituitary-gonadal axis. Understanding its precise regulation is key to developing novel strategies for reproductive control.

This review synthesizes evidence from studies in rhesus monkeys, goats, and genetically modified rodents to elucidate the neuroendocrine mechanisms governing the GnRH pulse generator activity. It examines the roles of kisspeptin, neurokinin B (NKB), and dynorphin A (Dyn), co-expressed in KNDy neurons, in generating rhythmic GnRH release. The review also integrates how diverse internal and external cues, including metabolic and neuroendocrine signals, modulate this critical reproductive axis, highlighting its potential as a therapeutic target.

The review establishes that KNDy neurons in the arcuate nucleus, co-expressing kisspeptin, neurokinin B, and dynorphin A, constitute the GnRH pulse generator. NKB is identified as a stimulatory factor, whereas Dyn exerts inhibitory effects, with their coordinated actions driving rhythmic GnRH secretion. > Pulsatile GnRH release is essential for normal reproductive function, as continuous administration has been shown to suppress pituitary responsiveness. The GnRH pulse generator integrates various signals: nutritional deficiency, inflammatory stress, and seasonal photoperiod suppress pulse frequency, while pheromonal stimuli (e.g., the male effect in ruminants) activate it. Central metabolic and neuroendocrine signals, including neuropeptide Y, cholecystokinin, melanocortin pathways, and serotonin, further modulate generator activity, thereby linking energy balance to reproductive function.