Polyamines: An Emerging Regulator of Gonadotropin Releasing Hormone (GnRH)

Particularly during ageing, the hypothalamic–pituitary–gonadal axis in mammals is governed by Gonadotropin-releasing hormone-I (GnRH-I), a fundamental neuropeptide. Polyamines are organic compounds with multiple amino groups. These are significant aliphatic amines that are expressed in the brain and show variations with ageing. As they are polycationic, they modulate the activity of negatively charged biomolecules such as DNA, RNA, proteins and phospholipids, thereby regulating various cellular and genetic functions. Correlations, both positive and negative, exist between polyamines, their associated factors, gonadotropin-releasing hormone (GnRH) and gonadotropin‐inhibitory hormone (GnIH). Notably, recent studies suggested polyamines enhance the activity of GnRH-I while simultaneously inhibiting GnIH. Polyamines also play a role in alternative splicing (AS). AS is significant for increasing the variety of the transcriptome and proteome, mainly in mammals. For example, putrescine has been shown to regulate the AS in the GnRH gene of the hypothalamus of rodents. While these findings highlight intriguing mechanisms, their translatability to humans remains to be clarified.