This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barber, K. J. Articles by Kilby, M. D. Search for Related Content PubMed PubMed Citation Articles by Barber, K. J. Articles by Kilby, M. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LIOTHYRONINE Related Collections Thyroid Female Endocrinology

The in Vitro Effects of Triiodothyronine on Epidermal Growth Factor-Induced Trophoblast Function

Divisions of Reproductive and Child Health (K.J.B., M.D.K.) and Medical Sciences (C.J.M., F.L.K., J.A.F.), The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Department of Biochemistry and Immunology (G.S.J.W.), St. George’s Hospital Medical School, London SW17 0RE, United Kingdom; and School of Clinical and Laboratory Science (J.N.B.), University of Newcastle, Newcastle upon Tyne NE1 4LP, United Kingdom

Address all correspondence and requests for reprints to: Professor Mark Kilby, Department of Maternal and Fetal Medicine, Division of Reproductive and Child Health, 3rd Floor, Birmingham Women’s Hospital, Edgbaston, Birmingham B15 2TG, United Kingdom. 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 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 in extravillous trophoblast, elucidate the effects of T₃ on both proliferation and differentiation of human trophoblast cells of varying origins, and define the potential interaction between EGF and T₃ on these processes. Using immunohistochemistry, specific thyroid hormone receptor 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 antiproliferative effect on an extravillous-like cell line (SGHPL-4) but stimulated proliferation in JEG-3 choriocarcinoma cells. EGF enhanced survival of nonproliferative 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.

This article has been cited by other articles:

				H. L. LaMarca, P. R. Dash, K. Vishnuthevan, E. Harvey, D. E. Sullivan, C. A. Morris, and G. St. J. Whitley Epidermal growth factor-stimulated extravillous cytotrophoblast motility is mediated by the activation of PI3-K, Akt and both p38 and p42/44 mitogen-activated protein kinases Hum. Reprod., August 1, 2008; 23(8): 1733 - 1741. [Abstract] [Full Text] [PDF]

				M.-R. Du, W.-H. Zhou, F.-T. Yan, X.-Y. Zhu, Y.-Y. He, J.-Y. Yang, and D.-J. Li Cyclosporine A induces titin expression via MAPK/ERK signalling and improves proliferative and invasive potential of human trophoblast cells Hum. Reprod., September 1, 2007; 22(9): 2528 - 2537. [Abstract] [Full Text] [PDF]

				S-Y Chan, J A Franklyn, H N Pemberton, J N Bulmer, T J Visser, C J McCabe, and M D Kilby Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction. J. Endocrinol., June 1, 2006; 189(3): 465 - 471. [Abstract] [Full Text] [PDF]

				M. Khare, A. H. Taylor, J. C. Konje, and S. C. Bell {Delta}9-Tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription Mol. Hum. Reprod., May 1, 2006; 12(5): 321 - 333. [Abstract] [Full Text] [PDF]

				H. E. M. zu Schwabedissen, M. Grube, A. Dreisbach, G. Jedlitschky, K. Meissner, K. Linnemann, C. Fusch, C. A. Ritter, U. Volker, and H. K. Kroemer EPIDERMAL GROWTH FACTOR-MEDIATED ACTIVATION OF THE MAP KINASE CASCADE RESULTS IN ALTERED EXPRESSION AND FUNCTION OF ABCG2 (BCRP) Drug Metab. Dispos., April 1, 2006; 34(4): 524 - 533. [Abstract] [Full Text] [PDF]