Estrogen effects on nigral glutamic acid decarboxylase activity: a possible role for catecholestrogen

Repeated but not single injections of estradiol benzoate significantly reduced nigral glutamic acid decarboxylase (GAD, EC 4.1.1.15). A single injection of the catecholestrogen 2-hydroxyestradiol produced similar results. Tolerance developed to the latter effect, as reflected by the lack of nigral GAD activity changes in rats repeatedly injected with 2-hydroxyestradiol. Repeated injection of the antiestrogen tamoxifen not only failed to antagonize the action of estradiol benzoate but itself reduced nigral GAD activity. Hypophysectomy, which itself decreased nigral GAD activity prevented the lowering effects of either repeated estradiol benzoate administration or single 2-hydroxyestradiol injection on the enzymatic activity.