Synthesis of thyroid hormone binding proteins transthyretin and albumin by human trophoblast.
BACKGROUND
Mechanisms regulating materno-fetal transfer of thyroid hormone are not well understood. Modulation of trophoblast type 3 iodothyronine deiodinase (D3) may play an important role.


OBJECTIVE
The objective of this study was to investigate trophoblast thyroid hormone binding proteins that may modulate interactions between D3 and T4.


METHODS
Placentas were obtained by informed consent from women delivering normal infants by repeat cesarean section at 38-40 wk gestation. T4 and T3 binding was examined in human placenta. Serum thyroid hormone binding proteins were identified by Western blotting, and their mRNA was examined by RT-PCR. Presence of these proteins in trophoblast was determined by immunocytochemistry and immunofluorescence. Cytosol was progressively purified to reveal additional thyroid hormone binding proteins that were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Effects of mefenamic acid on placental deiodination were examined by HPLC.


RESULTS
We detected high-affinity T4 and T3 binding in human placental cytosol. All three major serum-binding proteins, T4 binding globulin (TBG), transthyretin (TTR), and albumin, were present in cytosol. TTR mRNA and albumin mRNA were detected in human placenta, and TTR and albumin were identified histochemically in syncytiotrophoblasts. Neither TBG mRNA nor TBG was detected, suggesting that plasma TBG had contaminated the cytosol preparation. Low-affinity thyroid hormone binding proteins alpha-1-antitrypsin and alpha-1-acid glycoprotein were also identified. Addition of mefenamic acid, a potent inhibitor of thyroid hormone binding, to placental cytosol significantly enhanced deiodination of T4 by D3.


CONCLUSIONS
Placenta produces a series of thyroid hormone binding proteins that may modify thyroid hormone deiodination and materno-fetal thyroid hormone transport.
McKinnon
Brett
B
Conjoint Endocrine Laboratory, Clinical Research Centre, Royal Brisbane and Women's Hospital, Base Hospitals PO, Herston, Queensland 4029, Australia.
Li
Huika
H
Richard
Kerry
K
Mortimer
Robin
R
D000418:Albumins / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D010920:Placenta / Q000737:chemistry / Q000378:metabolism; D011228:Prealbumin / Q000096:biosynthesis* / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013963:Thyroid Hormones / Q000096:biosynthesis* / Q000302:isolation & purification; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
D000418:Albumins; D002352:Carrier Proteins; D008565:Membrane Proteins; D011228:Prealbumin; D012333:RNA, Messenger; D013963:Thyroid Hormones; D013974:Thyroxine; D014284:Triiodothyronine; D000097810:Thyroid Hormone-Binding Proteins