β-amyloid-induced gonadotropin-releasing hormone decline involving Forkhead transcription factor FOXO3a and nuclear factor-κB.

Previously, it has been demonstrated that aging is controlled by the hypothalamus, and that hypothalamus-driven programmatic aging is associated with nuclear factor-kappa B (NF-kappa B)-mediated gonadotropin-releasing hormone (GnRH) decrease. Abundant accumulation of beta-amyloid (A beta) has been observed in brains of cognitively normal elderly. However, it is unclear whether A beta neurotoxicity is involved in aging-associated hypothalamic GnRH decline. GT1-7 cells, which are a cell line of hypothalamic GnRH neurons, were used in the current study to investigate whether and how A beta decreased GnRH release. The results of the current study demonstrated that A beta impaired the release of GnRH through activation of NF-kappa B. Mechanistic studies revealed that A beta activated NF-kappa B via Forkhead box protein O3a, thereby inhibitinggnrh1gene. The results of the present study provided novel insights into the mechanisms underlying aging-dependent hypothalamic GnRH decline.