Carrier-Mediated Thyroid Hormone Transport into Placenta by Placental Transthyretin

Landers, Kelly A., McKinnon, Brett D., Li, Huika, Subramaniam, V. Nathan, Mortimer, Robin H. and Richard, Kerry (2009) Carrier-Mediated Thyroid Hormone Transport into Placenta by Placental Transthyretin. Journal of Clinical Endocrinology and Metabolism, 94 7: 2610-2616. doi:10.1210/jc.2009-0048


Author Landers, Kelly A.
McKinnon, Brett D.
Li, Huika
Subramaniam, V. Nathan
Mortimer, Robin H.
Richard, Kerry
Title Carrier-Mediated Thyroid Hormone Transport into Placenta by Placental Transthyretin
Journal name Journal of Clinical Endocrinology and Metabolism   Check publisher's open access policy
ISSN 0021-972X
Publication date 2009-07-01
Year available 2009
Sub-type Article (original research)
DOI 10.1210/jc.2009-0048
Open Access Status DOI
Volume 94
Issue 7
Start page 2610
End page 2616
Total pages 7
Place of publication Bethesda, MD, USA
Publisher Endocrine Society
Language eng
Subject 110306 Endocrinology
Abstract 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.
Formatted abstract
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.
Keyword Retinol-Binding-Protein
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 40 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 42 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 03 Sep 2009, 17:50:32 EST by Mr Andrew Martlew on behalf of Faculty Of Health Sciences