The role of the brain in female reproductive aging

摘要: In middle-aged women, follicular depletion is a critical factor mediating the menopausal transition; however, all levels of hypothalamic-pituitary-gonadal (HPG) axis contribute to age-related decline in reproductive function. To help elucidate complex interactions between ovary and brain during middle-age that lead onset menopause, we utilize animal models which share striking similarities physiology. Our results show middle-age, prior any overt irregularities estrous cyclicity, ability 17beta-estradiol (E(2)) modulate cascade neurochemical events required for preovulatory gonadotropin-releasing hormone (GnRH) release luteinizing (LH) surge diminished. Middle-aged female rats experience delay an attenuation LH response E(2). Additionally, although do not observe decrease GnRH neuron number until very advanced age, E(2)-mediated neuronal activation declines earliest stages decline. Numerous hypothalamic neuropeptides stimulatory inputs (i.e., glutamate, norepinephrine (NE), vasoactive intestinal peptide (VIP)) drive GnRH/LH appear dampen with age or lack precise temporal coordination specific pattern secretion, while inhibitory signals such as gamma-aminobutyric acid (GABA) opioid peptides remain unchanged elevated afternoon proestrus. These changes, occurring at level hypothalamus, irregular cycles and, ultimately, cessation Taken together, our studies indicate hypothalamus important contributor