Lévesque D, Di Paolo T
School of Pharmacy, Laval University, Québec, Canada.
Neurosci Lett. 1988 May 16;88(1):113-8. doi: 10.1016/0304-3940(88)90324-2.
Ovariectomized female rats injected with 17 beta-estradiol (100 ng, s.c.) showed, as previously observed, an increase of the dopamine (DA) metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) with no change of DA concentrations in the striatum. This increase was observed as soon as 15 min following the injection while plasma estradiol reached a peak of 78 pg/ml after 5 min and was significantly elevated until 45 min to ultimately return to control values at 60 min. We observed no significant change of the inhibition constants of high- and low-affinity D2 DA agonist binding sites and of the sum of high + low agonist DAergic agonist binding densities as detected by apomorphine competition of [3H]spiperone binding. By contrast, a significant conversion of high into low agonist affinity binding states was seen at 15 min (38.6% of conversion, P less than 0.05) and 30 min (40.0% of conversion, P less than 0.01) after the acute physiological steroid injection. Thus, very small doses of estradiol were able to rapidly increase DA turnover and modulate the striatal agonist affinity states of the D2 DA receptor. This effect of estradiol is probably non-genomic, presynaptic and may involve a membrane effect at the DA autoreceptor level.
如先前观察到的那样，皮下注射17β - 雌二醇（100纳克）的去卵巢雌性大鼠，纹状体内多巴胺（DA）代谢产物二羟基苯乙酸（DOPAC）和高香草酸（HVA）增加，而DA浓度无变化。注射后15分钟即可观察到这种增加，而血浆雌二醇在5分钟后达到78皮克/毫升的峰值，并在45分钟前显著升高，最终在60分钟时恢复到对照值。通过阿扑吗啡竞争[³H]螺哌隆结合检测，我们观察到高亲和力和低亲和力D2 DA激动剂结合位点的抑制常数以及高 + 低激动剂DA能激动剂结合密度之和均无显著变化。相比之下，在急性生理类固醇注射后15分钟（转化率为38.6%，P < 0.05）和30分钟（转化率为40.0%，P < 0.01）时，观察到高激动剂亲和力结合状态向低激动剂亲和力结合状态的显著转变。因此，非常小剂量的雌二醇能够迅速增加DA周转率并调节D2 DA受体的纹状体激动剂亲和力状态。雌二醇的这种作用可能是非基因组的、突触前的，并且可能涉及DA自身受体水平的膜效应。
