Some catecholamine inhibitors do not cause accumulation of nuclear estrogen receptors in rat hypothalamus and anterior pituitary gland.

Abstract

We have recently shown that the dopamine-beta-hydroxylase inhibitor, U-14,624, decreases the concentration of cytosol estrogen receptors in the mediobasal hypothalamus (MBH) and anterior pituitary gland (AP) in ovariectomized rats, but that it also causes cell nuclear accumulation of estrogen receptors. We tried to determine if this is the mechanism by which other catecholaminergic inhibitors decrease the concentration of cytosol estrogen receptors in either the MBH or AP. The previously reported decrease in the concentration of cytosol estrogen receptors in AP by the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine was confirmed. Also, the decrease in the concentration of cytosol estrogen receptors in MBH after treatment with the dopamine-beta-hydroxylase inhibitors, diethyldithiocarbamate and FLA 63 was demonstrated. In no case was an increase in the concentration of nuclear estrogen receptor accumulation detected after treatment with the drugs. Results of assays of norepinephrine and dopamine levels in MBH after the various treatments suggest that, at the dosage used, U-14,624 has a greater effect on norepinephrine and dopamine levels that the other dopamine-beta-hydroxylase inhibitors. The results of these experiments suggest that inhibitors of dopamine-beta-hydroxylase and tyrosine hydroxylase cause decreases in the concentration of cytosol estrogen receptors in either the MBH or AP that are not referable to increased cell nuclear accumulation of estrogen receptors.