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Estrogen receptor alpha (ERα) and insulin‐like growth factor I receptor (IGF‐IR) cross‐talk in the gonadotropic αT3‐1 cell line
Author(s) -
Eertmans Frank,
Dhooge Willem,
De Wever Olivier,
Bracke Marc,
Comhaire Frank,
Kaufman JeanMarc
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21053
Subject(s) - transactivation , endocrinology , medicine , estrogen receptor , biology , insulin like growth factor , estrogen receptor beta , estrogen receptor alpha , receptor , growth factor , transcription factor , biochemistry , gene , cancer , breast cancer
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 (E 2 ) 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 E 2 ‐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. J. Cell. Physiol. 212:583–590, 2007. © 2007 Wiley‐Liss, Inc.