Blum M, McEwen B S, Roberts J L
J Biol Chem. 1987 Jan 15;262(2):817-21.
The tuberoinfundibular dopaminergic neurons in the arcuate nucleus of the rat hypothalamus project to the median eminence and release dopamine from the axon terminals into the portal vessels. The released dopamine is transported to the anterior pituitary and acts to inhibit the release of prolactin from lactotrophs. About 50% of the tuberoinfundibular neurons have been shown to have estrogen receptors, and several research groups have shown that estrogen treatment affects dopamine release. Our interest is to determine, using an in vitro run-on transcription assay, whether acute estrogen treatment modulates the expression of the gene encoding for the rate-limiting enzyme for dopamine biosynthesis, tyrosine hydroxylase, in a manner parallel to the values reported for dopamine turnover. We found that after 20 min of estrogen treatment in a 3-week ovariectomized rat that tyrosine hydroxylase gene transcription decreased to 40% of control and continued to decrease after an hour of estrogen to 5% of control. After 4 days of estrogen, tyrosine hydroxylase gene transcription increased but was only about 70% of control. In contrast to the bimodal change in tyrosine hydroxylase gene transcription in response to acute estrogen, we were only able to detect a change in the levels of tyrosine hydroxylase mRNA after 2 weeks of estrogen treatment, when a 2-fold decrease was observed. Similar results for dopamine turnover, as compared to tyrosine hydroxylase gene transcription, have been reported by others in that 3 h after a single estrogen benzoate injection, dopamine turnover was decreased, while after 3 days there was not a significant change. Therefore, it seems that the changes in tyrosine hydroxylase gene transcription after acute estrogen treatment qualitatively parallel the values reported for dopamine turnover, suggesting that the rate of transcription may be an index of neural stimulation.
大鼠下丘脑弓状核中的结节漏斗多巴胺能神经元投射至正中隆起，并从轴突终末将多巴胺释放到门静脉血管中。释放的多巴胺被转运至垂体前叶，作用是抑制催乳素细胞释放催乳素。已证实约50%的结节漏斗神经元具有雌激素受体，并且几个研究小组已表明雌激素处理会影响多巴胺释放。我们感兴趣的是，使用体外连续转录测定法，确定急性雌激素处理是否以与多巴胺周转所报道的值平行的方式调节多巴胺生物合成限速酶酪氨酸羟化酶的编码基因的表达。我们发现，在对3周去卵巢大鼠进行20分钟雌激素处理后，酪氨酸羟化酶基因转录降至对照的40%，在雌激素处理1小时后继续降至对照的5%。雌激素处理4天后，酪氨酸羟化酶基因转录增加，但仅约为对照的70%。与急性雌激素作用下酪氨酸羟化酶基因转录的双峰变化相反，我们仅在雌激素处理2周后才检测到酪氨酸羟化酶mRNA水平的变化，此时观察到其降低了2倍。其他人报道了与酪氨酸羟化酶基因转录相比多巴胺周转的类似结果，即单次注射苯甲酸雌二醇3小时后，多巴胺周转降低，而3天后无显著变化。因此，急性雌激素处理后酪氨酸羟化酶基因转录的变化在质量上似乎与多巴胺周转所报道的值平行，这表明转录速率可能是神经刺激的一个指标。
