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This version published online on December 14, 2004
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-0785
A more recent version of this article appeared on March 1, 2005
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Submitted on April 28, 2004
Accepted on December 7, 2004

The in vitro effects of tri-iodothyronine on epidermal growth factor-induced trophoblast function

KJ Barber, JA Franklyn, CJ McCabe, FL Khanim, JN Bulmer, G. St J Whitley, JA Franklyn, and MD Kilby*

Division of Reproductive & Child Health (KJB; MDK), Division of Medical Sciences (FLK, CJM, JAF), The Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, Department of Biochemistry and Immunology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE (GSt.J W), School of Clinical and Laboratory Science, University of Newcastle, Newcastle upon Tyne, Newcastle, NE1 4LP (JNB)

* To whom correspondence should be addressed. E-mail: m.d.kilby{at}bham.ac.uk.

The development of the human placenta involves a complex process of tightly regulated proliferation and invasion by extravillous trophoblast into the uterine decidua. Inadequate placentation is a feature of intrauterine growth restriction and other gestational pathology. There is some evidence that tri-iodothyronine (T3) plays a role in the regulation of these processes, and that T3 may act synergistically with epidermal growth factor (EGF). The aim of this study was to define the expression of thyroid hormone receptors (TRs) in extravillous trophoblast, to elucidate the effects of T3 on both proliferation and differentiation of human trophoblast cells of varying origins, and to define the potential interaction between EGF and T3 on these processes. Using immunohistochemistry, specific TR isoforms were localized in extravillous trophoblast in first and second trimester placental bed biopsies, indicating potential sensitivity to T3. In studies of human trophoblast -derived cell lines and primary cultures of cytotrophoblast cells in vitro, T3 and EGF exerted an anti-proliferative effect on an extravillous-like cell line (SGHPL-4) but stimulated proliferation in JEG-3 choriocarcinoma cells. EGF enhanced survival of non-proliferative term primary cytotrophoblast cells and significantly enhanced invasion of fibrin gels by SGHPL-4 cells, an effect attenuated by T3. Both T3 and EGF also significantly enhanced SGHPL-4 motility. These results suggest that EGF and T3 may act synergistically to regulate both proliferation and differentiated function of human trophoblast.




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