Polyamine-Associated changes in circadian gene expression and their relationship to GnRH-I expression.

backgroundGonadotropin-releasing hormone (GnRH) plays a central role in regulating reproductive function. The rhythmic secretion of GnRH ensures that the pituitary gland receives precise signals to stimulate gonadal function, thereby promoting gametogenesis and steroidogenesis. The rhythmicity of GnRH secretion is modulated by circadian clock genes, such as Per1, Per2, Per3, Cry1, Cry2, Clock, Bmal1, and Csnk1e, which govern the timing of many physiological processes. Polyamines, particularly putrescine, have recently emerged as regulators of GnRH expression. It has also been shown that circadian genes are regulated by polyamines. However, the exact mechanisms through which polyamines modulate GnRH expression and their impact on the circadian regulation of reproductive timing remain unclear. Based on this, we hypothesize that polyamines may alter GnRH expression in relation to circadian clock gene activity. METHOD AND

resultqPCR analysis revealed a marked elevation in circadian gene mRNA levels in the adult hypothalamus, but these levels decreased significantly with aging. RNA sequencing analysis of GT1-7 cells treated with putrescine revealed significant upregulation in pathways associated with GnRH secretion, GnRH signaling, and circadian entrainment. Using hypothalamic GT1-7 cells treated with putrescine, we observed a concurrent upregulation of GnRH and core circadian genes in a temporal manner, with significant changes observed at 6-hour intervals. Correlation analysis further demonstrated that the mRNA expression of circadian genes was strongly and positively correlated with GnRH mRNA levels under putrescine treatment. Additionally, in an in vivo study the disruption of circadian rhythmicity in the hypothalamus was shown to abolish the inherent rhythmicity of both polyamines and GnRH expression, further highlighting the interplay between these systems.

conclusionThese findings provide novel insights into the link between polyamines, reproductive function, and circadian rhythms, specifically indicating that polyamines may influence GnRH expression in relation to circadian gene expression dynamics.Understanding this relationship could guide future studies aimed at uncovering the mechanisms by which polyamines regulate GnRH and may also open avenues for developing new approaches for addressing reproductive disorders linked to circadian disruptions and polyamine dysregulation.