The role of the brain in female reproductive aging.
The role of the brain in female reproductive aging.
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DOI：
10.1016/j.mce.2008.11.012
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发表时间：
2009-02-05
影响因子：
4.1
通讯作者：
Wise PM
中科院分区：
文献类型：
--
作者：
Downs JL;Wise PM
在中年女性中，卵泡耗竭是介导绝经过渡的关键因素;然而，下丘脑-垂体-性腺（HPG）轴的所有水平都有助于与年龄相关的生殖功能下降。为了帮助阐明中年时期卵巢和大脑之间复杂的相互作用导致更年期的发生，我们利用在生殖生理学方面具有惊人相似性的动物模型。我们的研究结果表明，在中年期间，在发情周期出现任何明显的不规则性之前，17β-雌二醇（E2）调节排卵前促性腺激素释放激素（GnRH）释放和促黄体激素（LH）激增所需的神经化学事件级联的能力减弱。中年雌性大鼠的经验延迟和衰减的LH释放响应E2。此外，虽然我们没有观察到GnRH神经元数量的减少，直到一个非常先进的年龄，E2介导的GnRH神经元激活下降，在早期阶段的年龄相关的生殖下降。许多下丘脑神经肽和神经化学刺激输入（即，驱动E2介导的GnRH/LH峰的谷氨酸、去甲肾上腺素（NE）和血管活性肠肽（VIP）似乎随着年龄的增长而减弱或缺乏特定GnRH分泌模式所需的精确时间协调，而抑制信号如γ氨基丁酸（GABA）和阿片肽在发情前期的下午保持不变或升高。这些变化发生在下丘脑水平，导致不规则的发情周期，最终导致生殖功能的停止。总之，我们的研究表明，下丘脑是一个重要的贡献者与年龄相关的女性生殖下降。
In middle-aged women, follicular depletion is a critical factor mediating the menopausal transition; however, all levels of the hypothalamic-pituitary-gonadal (HPG) axis contribute to the age-related decline in reproductive function. To help elucidate the complex interactions between the ovary and brain during middle-age that lead to the onset of the menopause, we utilize animal models which share striking similarities in reproductive physiology. Our results show that during middle-age, prior to any overt irregularities in estrous cyclicity, the ability of 17β-estradiol (E2) to modulate the cascade of neurochemical events required for preovulatory gonadotropin-releasing hormone (GnRH) release and a luteinizing hormone (LH) surge is diminished. Middle-aged female rats experience a delay in and an attenuation of LH release in response to E2. Additionally, although we do not observe a decrease in GnRH neuron number until a very advanced age, E2-mediated GnRH neuronal activation declines during the earliest stages of age-related reproductive decline. Numerous hypothalamic neuropeptides and neurochemical stimulatory inputs (i.e., glutamate, norepinephrine (NE), and vasoactive intestinal peptide (VIP) that drive the E2-mediated GnRH/LH surge appear to dampen with age or lack the precise temporal coordination required for a specific pattern of GnRH secretion, while inhibitory signals such as gamma aminobutyric acid (GABA) and opioid peptides remain unchanged or elevated during the afternoon of proestrus. These changes, occurring at the level of the hypothalamus, lead to irregular estrous cycles and, ultimately, the cessation of reproductive function. Taken together, our studies indicate that the hypothalamus is an important contributor to age-related female reproductive decline.
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影响因子：
4.8
作者：
EVERETT, JW;SAWYER, CH
通讯作者：
SAWYER, CH
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通讯作者：
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