Estrogen Receptor alpha (ERα) and Insulin-like Growth Factor I Receptor (IGF-IR) cross-talk in the gonadotropic αT3-1 cell line

Abstract

In reproductive tissues such as the breast and the uterus, cell proliferation and differentiation is strongly regulated by complex interactions between estrogen receptor α (ERα) and growth factor receptors. In the present study, we investigated the potential occurrence of such cross-talk in the murine, gonadotropic αT3-1 cell line, which expresses ERα and the IGF-I receptor (IGF-IR). Under estrogen-free conditions, basal cell proliferation and ER-mediated gene transcription was strongly inhibited by the selective estrogen receptor modulator (SERM) 4-hydroxy-tamoxifen (4-OH-Tam) and by the pure anti-estrogen ICI 182,780 (ICI). These effects can be reversed by either 17-β-estradiol (E2) or insulin-like growth factor I (IGF-I), both exerting modest mitogenic effects in the αT3-1 cell line. Furthermore, IGF-I enhanced both basal and E2-induced ER-driven gene transcription. This may be explained, at least in part, by enhanced phosphorylation of ERα at serine 118, a prerequisite for the transactivation capacity of the receptor. Finally, the IGF-I-induced response on cell growth and ER-mediated transactivation can be inhibited with either ICI or 4-OH-Tam. In conclusion, our data indicate IGF-IR and ER interactions in the αT3-1 cell line, an in vitro model for the pituitary gonadotrophs, hereby suggesting a role of IGF-I in the regulation of gonadotropin synthesis and secretion. © 2007 Wiley-Liss, Inc.