Transcriptional analysis of tyrosine hydroxylase gene expression in the tuberoinfundibular dopaminergic neurons of the rat arcuate nucleus after estrogen treatment

Abstract

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.