Dopamine-β-hydroxylase Inhibitors Modulate the Concentration of Functional Estrogen Receptors in Female Rat Hypothalamus and Pituitary Gland

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Abstract
In order to study further the regulation of steroid hormone receptors in the brain and anterior pituitary gland of ovariectomized rats by catecholamines, the influence of two dopamine-β-hydroxylase inhibitors on the estrogen receptor system was studied. The two inhibitors, FLA 63 and diethyldithiocarbamate (DDC) both caused a biphasic effect on the concentration of cytosol estrogen receptors in the mediobasal hypothalamus without influencing the concentration of cell nuclear estrogen receptors in the absence of estradiol; the concentration of cytosol estrogen receptors first increased and then decreased after treatment. In a study of the neuroanatomical areas in which inhibition of dopamine-β-hydroxylase decreases the concentration of cytosol estrogen receptors, it was found that the concentration of cytosol estrogen receptors decreased after drug treatment in the mediobasal hypothalamus and preoptic area-septum, but not in the amygdala. This suggests that the decrease in concentration of hypothalamic cytosol estrogen receptors caused by dopamine-β-hydroxylase inhibitors is not a nonspecific effect on all cytosol estrogen receptors. Finally, an injection of estradiol-17β in animals that had been pretreated with either DDC or FLA 63 resulted in less accumulation of cell nuclear estrogen receptors in those tissues in which the drug first caused a decrease in the concentration of cytosol estrogen receptors than in vehicle-injected controls. Therefore, under some conditions, pretreatment with a dopamine-β-hydroxylase inhibitor decreased the concentration of functional cytosol estrogen receptors resulting in decreased nuclear estrogen receptor accumulation in response to an estradiol injection. These results support the hypothesis that the catecholamines have a role in modulating the sensitivity to estradiol in some hypothalamic neurons and, in some circumstances, in the anterior pituitary gland.