Department of Obstetrics/Gynecology and Women's Health, Albert Einstein College of Medicine Bronx, NY, USA.
Front Endocrinol (Lausanne). 2012 Feb 22;3:24. doi: 10.3389/fendo.2012.00024. eCollection 2012.
Reproductive aging is characterized by delayed and attenuated luteinizing hormone (LH) surges apparent in middle-aged rats. The suprachiasmatic nucleus (SCN) contains the circadian clock that is responsible for the timing of diverse neuroendocrine rhythms. Electrophysiological studies suggest vasoactive intestinal peptide (VIP) originating from the SCN excites gonadotropin-releasing hormone (GnRH) neurons and affects daily patterns of GnRH-LH release. Age-related LH surge dysfunction correlates with reduced VIP mRNA expression in the SCN and fewer GnRH neurons with VIP contacts expressing c-fos, a marker of neuronal activation, on the day of the LH surge. To determine if age-related LH surge dysfunction reflects reduced VIP availability or altered VIP responsiveness under estradiol positive feedback conditions, we assessed the effect of intracerebroventricular (icv) VIP infusion on c-fos expression in GnRH neurons and on LH release in ovariohysterectomized, hormone-primed young and middle-aged rats. Icv infusion of VIP between 1300 and 1600 h significantly advanced the time of peak LH release, increased total and peak LH release, and increased the number of GnRH neurons expressing c-fos on the day of the LH surge in middle-aged rats. Surprisingly, icv infusion of VIP in young females significantly reduced the number of GnRH neurons expressing c-fos and delayed and reduced the LH surge. These observations suggest that a critical balance of VIP signaling is required to activate GnRH neurons for an appropriately timed and robust LH surge in young and middle-aged females. Age-related LH surge changes may, in part, result from decreased availability and reduced VIP-mediated neurotransmission under estradiol positive feedback conditions.
生殖衰老的特征是中年大鼠黄体生成素 (LH) 峰延迟和减弱。视交叉上核 (SCN) 包含生物钟，负责多种神经内分泌节律的时间安排。电生理学研究表明，源自 SCN 的血管活性肠肽 (VIP) 兴奋促性腺激素释放激素 (GnRH) 神经元，并影响 GnRH-LH 释放的日常模式。与 SCN 中 VIP mRNA 表达减少以及 GnRH 神经元减少相关的与 LH 峰相关的 LH 峰功能障碍与 VIP 接触表达 c-fos 的 GnRH 神经元减少有关，c-fos 是神经元激活的标志物，在 LH 峰当天。为了确定与年龄相关的 LH 峰功能障碍是否反映了 VIP 可用性降低或在雌二醇正反馈条件下 VIP 反应性改变，我们评估了脑室内 (icv) VIP 输注对 GnRH 神经元中 c-fos 表达和卵巢切除术、激素预处理的年轻和中年大鼠 LH 释放的影响。1300 至 1600 时 icv VIP 输注显着提前 LH 释放峰值时间，增加总 LH 释放和峰值 LH 释放，并增加 LH 峰当天表达 c-fos 的 GnRH 神经元数量。令人惊讶的是，年轻雌性动物中 icv VIP 输注显着减少了表达 c-fos 的 GnRH 神经元数量，并延迟和减少了 LH 峰。这些观察结果表明，在年轻和中年女性中，适当时间和强大的 LH 峰需要 VIP 信号的关键平衡。与年龄相关的 LH 峰变化可能部分是由于雌二醇正反馈条件下 VIP 可用性降低和减少的 VIP 介导的神经传递。
