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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/E331    most recent 00133.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chen, S. Articles by Kansra, S. PubMed PubMed Citation Articles by Chen, S. Articles by Kansra, S.

Epidermal growth factor receptor cross-talks with ligand-occupied estrogen receptor- to modulate both lactotroph proliferation and prolactin gene expression

²Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio; Departments of ¹Endocrinology, Metabolism and Clinical Nutrition and ³Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 2 March 2009 ; accepted in final form 21 May 2009

Both estrogen (E2) and EGF regulate lactotrophs, and we recently demonstrated that EGF phosphorylates S118 on estrogen receptor- (ER) and requires ER to stimulate prolactin (PRL) release. However, the interactions between ligand-occupied ER and activated ErbB1 and its impact on lactotroph function are unknown. Using rat GH3 lactotrophs, we found that both E2 and EGF independently stimulated proliferation and PRL gene expression. Furthermore, their combination resulted in an enhanced stimulatory effect on both cell proliferation and PRL gene expression. Inhibitors of ER as well as ErbB1 blocked the combined effects of E2 and EGF. Pretreatment with UO126 abolished the combined effects, demonstrating Erk1/2 requirement. Although bidirectionality in ER-ErbB1 cross-talk is a well-accepted paradigm, interestingly in lactotrophs, ErbB1 kinase inhibitor failed to block the effect of E2 on proliferation and stimulation of PRL gene expression, suggesting that ER does not require ErbB1 to mediate its effects. Furthermore, E2 did not affect the ability of EGF to induce c-Fos expression or modulate AP-1 activity. However, both E2 and EGF combine to enhance S118 phosphorylation of ER, leading to enhanced E2-mediated estrogen response element transactivation. Taken together, our results suggest that, in lactotrophs, activated ErbB1 phosphorylates ER to enhance the stimulatory effect of E2, thereby providing the molecular basis by which EGF amplifies the response of E2.

lactotrophs; cell proliferation