Time-dependent effects of estradiol and progesterone on the number of striatal dopaminergic D2-receptors

Abstract

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 (E 2) 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-E 2), which has been involved as local mediator in the effects of E 2, 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 E 2 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 E 2, in which administration of P produced an apparent increase 24 h after the steroid treatment. On the other hand, the 2-hydroxylated derivative of E 2 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. These results allow us to conclude that both sexual steroids have a dual effect on striatal dopaminergic receptors. Estradiol produced an inhibition followed by an increase in the density of these receptors in the striatum, which was not mediated by 2OH-E 2. Progesterone also caused an inhibition followed by a stimulation in the number of striatal dopaminergic receptors. However, the stimulatory effect needed the previous action of E 2, whereas the inhibition was only produced in animals non-pretreated with estrogens.