Fernández-Ruiz J J, Amor J C, Ramos J A
Department of Biochemistry, Faculty of Medicine, Complutense University, Madrid, Spain.
Brain Res. 1989 Jan 9;476(2):388-95. doi: 10.1016/0006-8993(89)91266-3.
Recent evidence has shown that sexual steroids are able to modify the activity of the dopaminergic nigrostriatal pathway. Most of this evidence has been obtained from the individual effects of these hormones, but there is less information about possible interrelationships between both. In order to further explore this question, ovariectomized adult rats were submitted to estradiol (E2) or vehicle injections during 3 days and, at the third day, were also submitted to a single injection of progesterone (P) or vehicle at 4, 10, 24 and 32 h before decapitation. Additionally, the effect of injections of 2-hydroxyestradiol (2OH-E2), which has been involved as local mediator in the effects of E2, was also examined. The two striata of each animal were removed and used for determination of number and affinity of dopamine D2-receptors, using [3H]spiroperidol as ligand. Administration of E2 produced a significant reduction in the number of striatal dopaminergic receptors 10 h after the last steroid injection, which was followed by an increase at 24 h. Administration of P briefly decreased the number of dopaminergic receptors at 4 h after the steroid injection. This effect was not observed in animals pretreated with E2, in which administration of P produced an apparent increase 24 h after the steroid treatment. On the other hand, the 2-hydroxylated derivative of E2 does not seem to mediate in the stimulatory action of this estrogen, since it was unable to increase the number of dopaminergic receptors by itself or priming the action of P. The affinity of dopaminergic receptors for [3H]spiroperidol was not significantly altered after all the steroid treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
近期证据表明,性类固醇能够改变多巴胺能黑质纹状体通路的活性。这些证据大多来自这些激素的个体效应,但关于两者之间可能的相互关系的信息较少。为了进一步探讨这个问题,对成年去卵巢大鼠在3天内注射雌二醇(E2)或溶剂,在第三天,在断头前4、10、24和32小时还分别注射一次孕酮(P)或溶剂。此外,还研究了作为E2效应局部介质的2-羟基雌二醇(2OH-E2)注射的效果。切除每只动物的两个纹状体,以[3H]螺哌啶醇为配体,用于测定多巴胺D2受体的数量和亲和力。最后一次注射类固醇后10小时,E2给药使纹状体多巴胺能受体数量显著减少,随后在24小时增加。类固醇注射后4小时,P给药使多巴胺能受体数量短暂减少。在用E2预处理的动物中未观察到这种效应,其中P给药在类固醇治疗后24小时使受体数量明显增加。另一方面,E2的2-羟基化衍生物似乎并未介导这种雌激素的刺激作用,因为它自身无法增加多巴胺能受体数量,也不能引发P的作用。所有类固醇治疗后,多巴胺能受体对[3H]螺哌啶醇的亲和力均未显著改变。(摘要截短于250字)