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  • Title: Modulation by estradiol and progesterone of the GTP effect on striatal D-2 dopamine receptors.
    Author: Lévesque D, Di Paolo T.
    Journal: Biochem Pharmacol; 1993 Feb 09; 45(3):723-33. PubMed ID: 8095140.
    Abstract:
    Agonist binding properties of rat striatal D-2 dopamine (DA) receptors were investigated after in vivo or in vitro estradiol or progesterone exposures in order to elucidate the mechanism of action of steroid hormones on DA receptors. Chronic estradiol treatment of ovariectomized rats (10 micrograms, twice each day, for 2 weeks) increased lateral striatum total receptor density and left unchanged the proportion and affinity of the agonist high- and low-affinity states of this receptor in the striatum. In addition, when GTP was added in DA competition for [3H]spiperone binding experiments, D-2 receptors in the medial part of the striatum from estrogen-treated animals were more sensitive to GTP than those in the lateral part, whereas GTP had equal activity in both parts of the striatum in vehicle-treated rats. With apomorphine, but not with DA competition for [3H]spiperone binding, addition of estradiol (1 nM) to striatal homogenates of intact male rats prevented the expected shift of the high- to the low-affinity state of D-2 receptors, normally induced by GTP (100 microM) under these conditions. This effect of estradiol was not observed in the presence of 4 mM MgCl2, while in vitro progesterone (100 nM) had no effect in either the absence or presence of MgCl2. In addition, in vivo chronic progesterone treatment of ovariectomized rats left striatal [3H]spiperone density and affinity unchanged. Moreover, 1 nM estradiol increased the IC50 of GTP for inhibition of [3H]N-propylnorapomorphine binding to the high-affinity state of striatal D-2 receptors. This effect was also observed but decreased by 2-fold in the presence of MgCl2. Our data suggest that estradiol in vivo and in vitro interferes with the effect of GTP on striatal D-2 DA receptors.
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