title: Synthesis of thyroid hormone binding proteins transthyretin and albumin by human trophoblast.
abstract: 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.
authors.affiliation: Conjoint Endocrine Laboratory, Clinical Research Centre, Royal Brisbane and Women's Hospital, Base Hospitals PO, Herston, Queensland 4029, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: McKinnon
authors.forename: Huika
authors.initials: H
authors.lastname: Li
authors.forename: Kerry
authors.initials: K
authors.lastname: Richard
authors.forename: Robin
authors.initials: R
authors.lastname: Mortimer
mesh_terms: 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
chemical_list: 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