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 Google Scholar Articles by Landers, K. A. Articles by Richard, K. PubMed PubMed Citation Articles by Landers, K. A. Articles by Richard, K. Related Collections Thyroid

Carrier-Mediated Thyroid Hormone Transport into Placenta by Placental Transthyretin

Conjoint Endocrine Laboratory (K.A.L., B.D.M., H.L., R.H.M., K.R.), Clinical Research Centre, Royal Brisbane and Women’s Hospital and Pathology Queensland, Herston, Queensland 4029, Australia; Membrane Transport Group (V.N.S.), Queensland Institute of Medical Research, Herston, Queensland 4006, Australia; and the Disciplines of Obstetrics and Gynaecology (R.H.M.) and Medicine (R.H.M., K.R.), The University of Queensland, St. Lucia, Queensland 4072, Australia

Address all correspondence and requests for reprints to: Kerry Richard, Conjoint Endocrine Laboratory, Bancroft Centre, 300 Herston Road, Herston, Queensland 4029, Australia. E-mail: kerry.richard{at}qimr.edu.au.

Context: The serum protein transthyretin (TTR) plays an important role in the transport of thyroid hormone and retinol, which are critical for normal development of the human fetus. TTR is not only synthesized and secreted into the circulation by the liver and other tissues but is also synthesized by placental trophoblasts, which separate the maternal and fetal circulations. Whether it is secreted or taken up by these cells and whether it carries thyroid hormone is unknown.

Objective and Methods: Our objective was to study placental handling of TTR and determine whether TTR participates in placental thyroid hormone transport. We investigated the capacity of human placenta and choriocarcinoma cell lines to secrete and internalize TTR and its ligands by Western blotting, immunofluorescence, and uptake of radiolabeled TTR.

Results: Human placental explants and TTR expressing JEG-3 cells secrete TTR. JEG-3 cells grown in bicameral chambers secrete TTR, predominantly from the apical surface. Human placental explants and JEG-3 cells internalize Alexa Fluor488-labeled TTR and ¹²⁵I-TTR. Furthermore, binding to thyroid hormones (T₄, T₃) increases ¹²⁵I-TTR uptake by enhancing tetramer formation. Cross-linking experiments confirm internalization of the TTR-¹²⁵I-T₄ complex.

Conclusions: Our results suggest that human placenta and choriocarcinoma cells secrete transthyretin, which binds extracellular T₄, and that T₄ binding results in increased internalization of TTR-T₄ complex. TTR production by trophoblasts may represent a mechanism to allow transfer of maternal thyroid hormone to the fetal circulation that could have important implications for fetal development.