Expression of polyamines and its association with GnRH-I in the hypothalamus during aging in rodent model.

Abstract

GnRH-I and GnIH are the key neuropeptides that regulate the hypothalamic-pituitary-gonadal axis in mammals during aging. Polyamines are important aliphatic amines that are expressed in the brain and show variation with aging. The present study demonstrates evidence of variation in the level of expression of polyamines, GnRH-I and GnIH in the hypothalamus of female mice during aging. The study also suggests regulatory effects of polyamines over expression of the hypothalamic GnRH-I. The study shows a significant positive correlation between polyamines, its associated factors and GnRH-I along with significant negative correlation between polyamines, its associated factors and GnIH. This is the first study to report the effect of polyamines along with lactate or TNF-α or both on GnRH-I expression in GT1-7 cell line. TNF-α and lactate significantly decreased hypothalamic GnRH-I mRNA expression in GT1-7 cells when treated for 24h. Polyamines (putrescine and agmatine) in contrast, significantly increased GnRH-I mRNA expression in GT1-7 cells when treated for 24h. Also, polyamines increased GnRH-I mRNA expression when treated in presence of TNF-α or lactate thereby suggesting its neuro-protective role.This study also found 3809 differentially expressed genes through RNA-seq done between the hypothalamic GT1-7 cells treated with putrescine only versus TNF-α and putrescine. The present study suggests for the first time that putrescine treatment to TNFα-primed GT1-7 cells upregulates GnRH-I expression via regulation of several pathways such as calcium ion pathway, estrogen signaling, clock genes as well as regulating other metabolic process like neuronal differentiation and neurulation.