Role of the Maternal Carrier Proteins in the Supply of Thyroid Hormones to the Feto-Placental Unit: Evidence of a Feto-Placental Requirement for Thyroxine

  • Roger Ekins
  • Arun Sinha
  • Maria Ballabio
  • Mark Pickard
  • Michael Hubank
  • Zaidan al Mazidi
  • Mohamed Khaled
Part of the NATO ASI Series book series (NSSA, volume 161)


For a number of years, the consensus view amongst endocrinologists has been that thyroid hormones of maternal origin neither cross the placenta in significant amount1, nor are implicated in the development of the fetus in general, or of the fetal CNS in particular2. Nevertheless, for a number of reasons (some of which have been discussed in3), the validity of this view appeared to us to be open to doubt; we therefore initiated studies (ca 1980) specifically intended to verify or disprove some of the experimental evidence and theoretical postulates on which this view was based.


Thyroid Hormone Thyroxine Binding Globulin Free Hormone Hormone Transport Adult Progeny 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fisher, D. A., J. K. Dussault, J. Sack and I. J. Chopra, Ontogenesis of hypothalamicpituitary-thyroid function and metabolism in man, sheep and rat, jp: “Recent Progress in Hormone Research”, R. O. Greep, ed., Academic Press, New York (1977).Google Scholar
  2. 2.
    Nunez, J., Effects of thyroid hormones during brain differentiation, Mol. Cell. Endocrinol. 37:125 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    Ekins, R. P., Hypothesis: The roles of serum thyroxine binding proteins and maternal thyroid hormones in foetal development Lancet (i): 1129 (1985).Google Scholar
  4. 4.
    Sinha, A., Woods R., Ekins R. P., Thyroxine metabolism by maternal and foetal tissues in the rat in early pregnancy Ann d’Endocrinol44: 9A (1983).Google Scholar
  5. 5.
    Osorio, C. and N. B. Myant, The passage of thyroid hormones from mother to foetus and its relation to foetal development, Brit. Med. Bull. 16:159 (1960).PubMedGoogle Scholar
  6. 6.
    Robbins, J., and J. E. Rail, Thyroid hormone transport in blood and extravascular fluids, in: “Hormones in Blood”, C. H. Gray and V. H. T. James, eds., Academic Press, London (1979).Google Scholar
  7. 7.
    Tait, J. F. and S. Burstein, In vivo studies of steroid dynamics in man, in: “The Hormones”, vol. V, Pincus, K. V. Thimann and E. B. Astwood, eds., Academic Press, New York, (1964).Google Scholar
  8. 8.
    Keller, N., U. I. Richardson and F. E. Yates, Protein binding and the biological activity of corticosteroids: in vivo induction of hepatic and pancreatic alanine aminotransferases by corticosteroids in normal and estrogen treated rats Endocrinology 84: 49 (1969).Google Scholar
  9. 9.
    Siiteri, P. K., J. T. Murai, G. L. Hammond, J. A., Nicker, W. J. Raymoure and R. W. Kuhn, The serum transport of steroid hormones, in: “Recent Progress in Hormone Research”, R. O. Greep, ed., Academic Press, New York, (1982).Google Scholar
  10. 10.
    Pardridge, W. M., Transport of protein-bound hormones into tissues in vivo Endocr. Rev. 2:102 (1981).Google Scholar
  11. 11.
    Pardridge, W. M., Transport of protein-bound thyroid and steroid hormones into tissues in vivo: a new hypothesis on the role of hormone binding plasma proteins, in: “Free Hormones in Blood”, A. Albertini and R. P. Ekins, eds., Elsevier/North Holland, Amsterdam (1982).Google Scholar
  12. 12.
    Pardridge, W. M., Plasma protein-mediated transport of steroid and thyroid hormones, Ara,_ J. Physiol. 252 (Endocrinol. Metab.15):E157 (1987).Google Scholar
  13. 13.
    Ekins R. P. and P. R. Edwards, Plasma protein-mediated transport of steroid and thyroid hormones: a critique, Ann. N.Y. Acad. Sc(. (in press).Google Scholar
  14. 14.
    Ekins, R. P., P. R. Edwards, and B. Newman, The role of binding proteins in hormone delivery, in: “Free Hormones in Blood”, A. Albertini and R. P. Ekins, eds., Elsevier/North Holland, Amsterdam (1982).Google Scholar
  15. 15.
    Pardridge, W. M. and E. M. Landaw, Tracer kinetic model of blood-brain barrier transport of plasma protein-bound ligands. Empiric testing of the free hormone hypothesis. J. Clin. Invest. 74:745 (1984).Google Scholar
  16. 16.
    Ekins, R. P., The free hormone concept, in: “Thyroid hormone metabolism”, G. Hennemann, ed., Marcel Dekker, New York (1985).Google Scholar
  17. 17.
    Seal, V. S. and R. P. Doe, Corticosteroid-binding globulin: biochemistry, physiology and phylogeny, in: “Steroid dynamics”, G. Pincus, T. Nadao and J. F.Tait, eds., Academic Press, New York (1966).Google Scholar
  18. 18.
    Obregon, M. J., J. Mallol, R. Pastor, G. Morreale de Escobar and F. Escobar del Rey, L-Thyroxine and 3,5,3’-Triiodo-L-Thyronine in rat embryos before onset of foetal thyroid function Endocrinology 114: 305 (1984).Google Scholar
  19. 19.
    Pharoah, P. 0.D., I. H. Buttfield and B. S. Hetzel, The effect of iodine prophylaxis on the incidence of endemic cretinism, Advances in Exp. Med. and Bio(. 30:201 (1972).Google Scholar
  20. 20.
    Morreale de Escobar,G., M.. Obregon and C. R. Ona, Comparison of maternal to fetal transfer of T3 versus T4 in rats, as assessed by T3 levels in fetal tissues. Ann. d’Endocrirt. 48: 165 (1987).Google Scholar
  21. 21.
    Ekins R. P., Woods R. J., Sinha A. K., Maternal thyroid hormones and development of the fetal brain, in: “Iodine nutrition, thyroxine and brain development”, N. Kochpillai and V. Ramalingaswami, eds.,Tata McGraw Hill, New Delhi (1986).Google Scholar
  22. 22.
    Devaskar U. P., S. U. Devaskar, H. Farouk Sadig, V. Chechani, Ontogeny of plasma-free thyroxine and triiodothyronine concentrations during the perinatal period and maternofetal transfer of thyroid hormones in the rabbit Dev. Pharmaco(. Ther. 9:115 (1986).Google Scholar
  23. 23.
    Carayon P., Lefort G. and B. Nisula, Interaction of human chorionic gonadotropin and human luteinizing hormone with human thyroid membranes, Endocrinology 106: 1907 (1980).Google Scholar
  24. 24.
    Ballabio M., Sinha A. K. and R. P. Ekins, Thyrotropic activity of crude hCG in FRTL-5 rat thyroid cells Acta Endocrinologica 116: 479 (1987).Google Scholar
  25. 25.
    Hubank M., Ballabio M., Sinha A. K., Gullo D., Bidey S., Bashir A., Ekins R. P., Long-term effects of maternal thyroidectomy on the development of the central nervous system of the progeny in the rat Ann. d’Endocrinol. 47: 48 (1986).Google Scholar
  26. 26.
    Pickard M. R., A. K. Sinha, D. Gullo, N. Patel, M. Hubank, R. P. Ekins, The effect of 3,5,3’triiodothyronine on leucine uptake and incorporation into protein in cultured neurons and subcellular fractions of rat central nervous system, Endocrinoloay 121: 2018 (1987).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Roger Ekins
    • 1
  • Arun Sinha
    • 1
  • Maria Ballabio
    • 1
  • Mark Pickard
    • 1
  • Michael Hubank
    • 1
  • Zaidan al Mazidi
    • 1
  • Mohamed Khaled
    • 1
  1. 1.Department of Molecular EndocrinologyUniversity College and Middlesex School of Medicine University of LondonLondonUK

Personalised recommendations