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Synthesis of Thyroid Hormone Binding Proteins Transthyretin and Albumin by Human Trophoblast

Conjoint Endocrine Laboratory (B.M., H.L., K.R., R.M.), Clinical Research Centre, Royal Brisbane and Women’s Hospital and Queensland Health Pathology Services, Herston, Queensland 4029, Australia; and the Department of Obstetrics and Gynaecology (R.M.), The University of Queensland, St. Lucia, Queensland 4072, Australia

Address all correspondence and requests for reprints to: Dr. Robin Mortimer, Department of Endocrinology, Royal Brisbane and Women’s Hospital, Base Hospitals PO, Herston, Queensland 4029, Australia. E-mail: robin_mortimer{at}health.qld.gov.au.

Context: 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.

Design: 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 -1-antitrypsin and -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.

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