Abstract
In the pituitary, estrogen induces lactotroph proliferation and prolactin (PRL) secretion, and long term exposure to estrogen leads to prolactinoma formation. Dopamine (DA) is a well-known inhibitory agent on lactotrophs and affects estrogen-induced lactotroph proliferation. However, the molecular mechanism of the inhibitory action of dopamine is still not clear. In this study, we examined whether DA influences transcriptional activity of estrogen response element (ERE), a target sequence for activated estrogen receptor, in lactotrophs in primary cuture. To determine the lactotroph-specific ERE activity, we developed an adenovirus-mediated reporter assay system in which PRL promoter drives expression of an ERE reporter gene via Cre/loxP system. We found that estrogen-stimulated ERE activity in lactotrophs was inhibited by bromocriptine (BC) as well as DA treatment. Same results were obtained using a combination of discontinuous Percoll gradient-enriched lactotrophs and an ERE reporter assay without Cre/loxP system. The DA action was through D2 dopamine receptor activation because the BC-induced inhibition was reversed by treament with a selective D2 dopamine receptor antagonist and a D1 dopamine receptor agonist failed to inhibit the ERE activity. The BC-induced inhibition of ERE activity was not accompanied by a decrease in ERα protein and mRNA expression, suggesting that the recruitment of coregulators is negatively influenced by DA. These results indicate that there is an inhibitory crosstalk between ERE and D2 dopamine receptor activation in pituitary lactotrophs. [J Physiol Sci. 2008;58 Suppl:S139]
