Blaustein J D, Brown T J, McElroy J F
Neuroendocrinology. 1986;43(2):143-9. doi: 10.1159/000124521.
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.
我们最近发现，多巴胺-β-羟化酶抑制剂U-14,624可降低去卵巢大鼠中脑基底下丘脑（MBH）和垂体前叶（AP）中胞质雌激素受体的浓度，但它也会导致雌激素受体在细胞核内蓄积。我们试图确定这是否是其他儿茶酚胺能抑制剂降低MBH或AP中胞质雌激素受体浓度的机制。酪氨酸羟化酶抑制剂α-甲基-对-酪氨酸可降低AP中胞质雌激素受体浓度，这一结果得到了之前报道的证实。此外，还证实了用多巴胺-β-羟化酶抑制剂二乙基二硫代氨基甲酸盐和FLA 63处理后，MBH中胞质雌激素受体浓度降低。在用这些药物处理后，均未检测到核雌激素受体蓄积浓度增加。各种处理后对MBH中去甲肾上腺素和多巴胺水平的测定结果表明，在所使用的剂量下，U-14,624对去甲肾上腺素和多巴胺水平的影响比其他多巴胺-β-羟化酶抑制剂更大。这些实验结果表明，多巴胺-β-羟化酶和酪氨酸羟化酶抑制剂可降低MBH或AP中胞质雌激素受体的浓度，这与雌激素受体在细胞核内蓄积增加无关。
