Krajnak K, Rosewell K L, Wise P M
Department of Biology, West Virginia University, Morgantown, West Virginia 26506, USA.
Biol Reprod. 2001 Apr;64(4):1160-4. doi: 10.1095/biolreprod64.4.1160.
A hallmark of reproductive aging in rats is a delay in the initiation and peak, and a decrease in the amplitude, of both proestrous and steroid-induced surges of LH and a decrease in the number of GnRH neurons that express Fos during the surge. The altered timing of the LH surge and the decline in Fos expression in GnRH neurons may be due to changes in the rhythmic expression of vasoactive intestinal polypeptide (VIP), a neuropeptide that carries time-of-day information from the circadian pacemaker, located in the suprachiasmatic nuclei (SCN), to GnRH neurons. The goals of our study were to determine if aging alters 1) the innervation of GnRH neurons by VIP and 2) the ability of VIP to activate GnRH neurons by examining the effects of aging on the number of GnRH neurons apposed by VIP fibers and the number of GnRH neurons that receive VIP input that express Fos. Immunocytochemistry for GnRH and VIP; or GnRH, VIP, and Fos was performed on tissue sections collected from young (2-4 mo), regularly cycling females and middle-aged (10-12 mo) females in constant estrus. The number of GnRH neurons, GnRH neurons apposed by VIP fibers, and GnRH neurons that express Fos and apposed by VIP fibers were counted in both age groups. Our results clearly demonstrate that aging does not alter the number of GnRH neurons that receive VIP innervation. However, the number of GnRH neurons that receive VIP innervation and coexpress Fos decreases significantly. We conclude that the age-related delay in the timing of the LH surge is not due to a change in VIP innervation of GnRH neurons, but instead may result from a decreased sensitivity of GnRH neurons to VIP input.
大鼠生殖衰老的一个标志是动情前期以及促性腺激素释放激素（GnRH）神经元在LH峰期间表达Fos数量的变化，即起始时间和峰值延迟、幅度减小。LH峰时间的改变以及GnRH神经元中Fos表达的下降，可能是由于血管活性肠肽（VIP）节律性表达的变化所致。VIP是一种神经肽，它将昼夜节律起搏器（位于视交叉上核，SCN）的昼夜时间信息传递给GnRH神经元。我们研究的目的是通过检查衰老对与VIP纤维相邻的GnRH神经元数量以及接受VIP输入并表达Fos的GnRH神经元数量的影响，来确定衰老是否会改变1）VIP对GnRH神经元的神经支配，以及2）VIP激活GnRH神经元的能力。对从年轻（2 - 4个月）、处于正常发情周期的雌性大鼠和中年（10 - 12个月）、处于持续发情期的雌性大鼠收集的组织切片进行GnRH和VIP；或GnRH、VIP和Fos的免疫细胞化学检测。在两个年龄组中分别计数GnRH神经元的数量、与VIP纤维相邻的GnRH神经元数量，以及表达Fos且与VIP纤维相邻的GnRH神经元数量。我们的结果清楚地表明，衰老不会改变接受VIP神经支配的GnRH神经元数量。然而，接受VIP神经支配并共表达Fos的GnRH神经元数量显著减少。我们得出结论，与年龄相关的LH峰时间延迟不是由于GnRH神经元的VIP神经支配发生变化，而是可能源于GnRH神经元对VIP输入的敏感性降低。
