Carrier-mediated thyroid hormone transport into placenta by placental transthyretin.
BACKGROUND
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
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 (125)I-TTR. Furthermore, binding to thyroid hormones (T(4), T(3)) increases (125)I-TTR uptake by enhancing tetramer formation. Cross-linking experiments confirm internalization of the TTR-(125)I-T(4) complex.


CONCLUSIONS
Our results suggest that human placenta and choriocarcinoma cells secrete transthyretin, which binds extracellular T(4), and that T(4) binding results in increased internalization of TTR-T(4) 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.
Landers
Kelly A
KA
Conjoint Endocrine Laboratory, Bancroft Centre, Royal Brisbane and Women's Hospital and Pathology Queensland, Herston, Queensland 4029, Australia.
McKinnon
Brett D
BD
Li
Huika
H
Subramaniam
V Nathan
VN
Mortimer
Robin H
RH
Richard
Kerry
K
D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D009924:Organ Culture Techniques; D010920:Placenta / Q000378:metabolism*; D021041:Placental Circulation / Q000502:physiology; D011228:Prealbumin / Q000378:metabolism* / Q000502:physiology*; D011247:Pregnancy; D013963:Thyroid Hormones / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology
D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D007457:Iodine Radioisotopes; D011228:Prealbumin; D013963:Thyroid Hormones