Dysregulation of the hypothalamic-pituitary-gonadal axis with menopause and andropause promotes neurodegenerative senescence.

摘要: Senescence is characterized neurologically by a decline in cognitive function, which we propose the result of degenerative processes initiated dysregulation hypothalamic-pituitary-gonadal (HPG) axis with menopause and andropause. Compelling epidemiologic evidence to support this assertion includes increased prevalence Alzheimer disease (AD) women, correlation serum HPG hormones decreased incidence, delay onset AD following hormone replacement therapy. Dysregulation at time leads alterations concentrations all (decreased neuronal sex steroid signaling, but gonadotropin releasing hormone, luteinizing activin signaling). Hormones axis, receptors for are present adult brain, important regulators cell proliferation differentiation during growth development. Based on this, that dysregulated signaling menopause/andropause abortive reentry differentiated neurons into cycle via process term "dyosis." Interestingly, major biochemical neuropathologic changes reported brain also intimately associated neuron division: altered AβPP metabolism, Aβ deposition, tau phosphorylation, mitochondrial alterations, chromosomal replication, synapse loss, death neurons. Recent supports premise AD-related likely combined mitotic gonadotropins GnRH, differentiative neuroprotective steroids, activins. This results hormonal milieu permissive does not allow completion metaphase. Partial resetting administration normal endogenous steroids delays decreases incidence AD. Ideally, supplementation should mimic closely reproductive men cycling women prevent dyotic attempted division.