Hypothalamic reproductive neurons communicate through signal transduction to control reproduction.

Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus coordinate fertility and puberty. In order to achieve successful reproductive capacity, they receive signals from the periphery and from other hypothalamic neurons that coordinate energy homeostasis. Hormones, such as estradiol, insulin, leptin, and adiponectin, act directly or indirectly on GnRH and its associated reproductive neurons. Nutrients like glucose and fatty acids can also affect reproductive neurons to signal nutrient availability. Additionally, acute and chronic inflammation is reported to detrimentally affect GnRH and kisspeptin expression. All of these cues activate signal transduction pathways within neurons that lead to the changes in GnRH neuronal function. The signalling pathways can also be dysregulated by endocrine disrupting chemicals, which impair fertility by misappropriating common signalling pathways. The complex mechanisms controlling the levels of GnRH during the reproductive cycle rely on a carefully orchestrated set of signal transduction events to regulate the positive and negative feedback arms of the hypothalamic-pituitary-gonadal axis. If these signalling events are dysregulated, this will result is a downregulatory event leading to hypogonadal hypogonadism with decreased or absent fertility. Therefore, an understanding of the mechanisms involved in distinct neuronal signalling could provide an advantage to inform therapeutic interventions for infertility and reproductive disorders.