Gregerson K A, Selmanoff M
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201.
Endocrinology. 1990 Jan;126(1):228-34. doi: 10.1210/endo-126-1-228.
The release of preaccumulated tritium-labeled dopamine [( 3H]DA) was examined in isolated nerve terminals (synaptosomes) prepared from the median eminence (ME) and corpus striatum (CS) of young (2-3 months), middle-aged (11-12 months), and old (19-21 months) male rats. Fractional release of [3H]DA was measured over 1- to 10-sec time intervals under basal (5 mM K+) and depolarizing (75 mM K+) conditions in the presence of calcium. No differences in the rate of basal efflux between the age groups were observed in either ME or CS preparations. Fast-phase evoked [3H]DA release (0-1 sec) from CS synaptosomes was unchanged from young to middle-aged, but was decreased in old preparations. These data demonstrate that the nigrostriatal nerve terminal has a diminished ability to respond fully to depolarizing stimuli in advanced age. Mean serum PRL levels in old rats were 2.3-fold greater than those in both young and middle-aged rats, while serum LH levels were decreased 2.0-fold in middle-aged and old compared with those in young rats. The fact that LH levels were already decreased in middle-aged rats while PRL levels had not yet increased suggests that decreased gonadotropin titers in old rats do not result from the coincident hyperprolactinemia. In ME synaptosomes, depolarization-induced [3H]DA release was decreased at all time points in middle-aged preparations compared to that in young preparations. The reduced fractional release from the middle-aged ME synaptosomes was due to a depressed rate of release during the initial second of depolarization. Evoked release from ME terminals of old rats was comparable to that measured in the young group. Thus, there occurred an age-related biphasic change in the initial rate of evoked DA release from ME synaptosomes. Diminished response of ME dopaminergic terminals to depolarizing stimuli during middle age may be important in the later development of hyperprolactinemia in aging male rats. The increased PRL available for feedback on the tuberoinfundlbular dopaminergic neurons may, in turn, be associated with the apparent recovery of evoked [3H]DA release from ME synaptosomes of old rats.
研究了从年轻（2 - 3个月）、中年（11 - 12个月）和老年（19 - 21个月）雄性大鼠的正中隆起（ME）和纹状体（CS）制备的离体神经末梢（突触体）中预先积累的氚标记多巴胺[（3H）DA]的释放情况。在存在钙的基础（5 mM K +）和去极化（75 mM K +）条件下，在1至10秒的时间间隔内测量[3H]DA的分数释放。在ME或CS制剂中，未观察到各年龄组之间基础流出率的差异。CS突触体的快速相诱发[3H]DA释放（0 - 1秒）从年轻到中年没有变化，但在老年制剂中减少。这些数据表明，黑质纹状体神经末梢在高龄时对去极化刺激做出充分反应的能力减弱。老年大鼠的平均血清PRL水平比年轻和中年大鼠高2.3倍，而中年和老年大鼠的血清LH水平与年轻大鼠相比降低了2.0倍。中年大鼠LH水平已经降低而PRL水平尚未升高这一事实表明，老年大鼠促性腺激素滴度降低并非由同时发生的高催乳素血症所致。在ME突触体中，与年轻制剂相比，中年制剂在所有时间点去极化诱导的[3H]DA释放均减少。中年ME突触体分数释放减少是由于去极化最初一秒内释放速率降低。老年大鼠ME末梢的诱发释放与年轻组测量的结果相当。因此，ME突触体诱发DA释放的初始速率出现了与年龄相关的双相变化。中年时ME多巴胺能末梢对去极化刺激的反应减弱可能在衰老雄性大鼠高催乳素血症的后期发展中起重要作用。可用于对结节漏斗多巴胺能神经元进行反馈的PRL增加，反过来可能与老年大鼠ME突触体诱发[3H]DA释放的明显恢复有关。
