Regulation of Intracellular Thyroid Hormone Concentrations in the Fetus

  • Maria Jesús Obregón
  • Carmen Ruiz de Oña
  • Francisco Escobar del Rey
  • Gabriella Morreale de Escobar
Part of the NATO ASI Series book series (NSSA, volume 161)


Thyroid hormones play an important role in development1, especially in brain development2, 3. The role of thyroid hormones in development include the stimulation of skeletal maturation, the diferentiation of central nervous system, and they seem to regulate other processes such as the maturation of lung and the process of non-shivering thermogenesis in the neonate. Most of the information available is based on experimental models, mainly in the rat and sheep, due to the obvious difficulties to examine the effects of thyroid hormone deficiency in the human developing brain.


Thyroid Hormone Brown Adipose Tissue Fetal Brain Congenital Hypothyroidism Fetal Plasma 
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  1. 1.
    Legrand, J., Thyroid hormone effects on growth and development, in “Thyroid Hormone Metabolism”, G. Hennemann, Marcel Dekker, New York & Basel, (1986), p 503.Google Scholar
  2. 2.
    Morreale de Escobar, G., A. Ruiz-Marcos and F. Escobar del Rey, Thyroid hormones and the developing brain, in: “Congenital Hypothyroidism”, J. Dussault and P. Walker, eds., Marcel Dekker, New York (1983), p 85.Google Scholar
  3. 3.
    Rosman, N.P. and M. J. Malone, Brain myelination in experimental hypothyroidism: Morphological and biochemical observations, in: “Thyroid Hormones and the Developing Brain”, G. D. Grave, ed., Raven Press, New York (19) p 169.Google Scholar
  4. 4.
    Fisher, D.A.,J. H. Dussault, J. Sack, I. J. Chopra, Onto-genesis of hypothalamic-pituitary-thyroid function and metabolism in man, sheep and rat, Rec Prog. Horm. Res. 33: 59 (1977).Google Scholar
  5. 5.
    Wrutniak C. and G. Cabello, Changes in the concentration of thyroxine in the plasma of rat fetuses during late gestation: influence of ligation of the maternal uterine vein and artery, J. Endocrinol (London) 99: 233 (1983)Google Scholar
  6. 6.
    Harris, A. R.C., S. L. Fang, J. Prosky, L. E. Braverman and A. G. Vagenakis, Decreased outer ring monodeiodination of thyroxine and reverse triiodothyronine in the fetal and neonatal rat, Endocrinology 103: 2216 (1978)PubMedCrossRefGoogle Scholar
  7. 7.
    Cheron, R. G., M. M. Kaplan and P. R. Larsen, Divergent changes of thyroxine-5’-monodeiodination in rat pituitary and liver during maturation, Endocrinology 106: 1405 (1980)PubMedCrossRefGoogle Scholar
  8. 8.
    El-Zaheri, M. M., L. E. Braverman and A. G. Vagenakis, Enhanced conversion of thyroxine to triiodothyronine by the neonatal rat pituitary, Endocrinology 106: 1735 (1980)PubMedCrossRefGoogle Scholar
  9. 9.
    Kaplan, M. M. and K. A. Yaskoski, Maturational patterns of iodothyronine phenolic and tyrosyl ring deiodinase activities in rat cerebrum, cerebelum and hypothalamus, J. Clin. Invest. 67: 1208 (1981).PubMedCrossRefGoogle Scholar
  10. 10.
    Suzuki, Y., K. Kita, Y. Uchigata, I. Takata and T. Sato, Maturation of renal and hepatic monodeiodination of thyroxine to triiodothyronine and post-natal changes of serum thyroid hormones in young rats, Acta Endocrinologica 99: 540 (1982).PubMedGoogle Scholar
  11. 11.
    Kaplan, M. M. and K. A. Yaskoski, Effects of congenital hypothyroidism and partial and complete food deprivation on phenolic and tyrosyl ring iodothyronine deiodination in rat brain, Endocrinology 110: 761 (1982).PubMedCrossRefGoogle Scholar
  12. 12.
    Obregon, M. J., J. Mallol, R. Pastor, G. Morreale de Escobar and F. Escobar del Rey, L-Thyroxine and 3,5,3’- triiodothyronine in rat embryos before onset of fetal thyroid function, Endocrinology 114: 305 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    Morreale de Escobar, G., R. Pastor, M. J. Obregón and F. Escobar del Rey, Effects of maternal hypothyroidism on the weight and thyroid hormone content of rat embryonic tissues, before and after onset of fetal thyroid function, Endocrinology 117: 1890 (1985).CrossRefGoogle Scholar
  14. 14.
    Woods, R. J., A. K. Sinha and R. P. Ekins, Uptake and metabolism of thyroid hormones by the rat foetus in early pregnancy, Clinical Science 67: 359 (1984).PubMedGoogle Scholar
  15. 15.
    Roti, E., L. E. Braverman, S-L. Fang, S. Alex and C. H. Emerson, Ontogenesis of placental inner ring thyroxine deiodinase and amniotic fluid 3,3’,5’-triiodothyronine concentration in the rat, Endocrinology 111: 959 (1982).PubMedCrossRefGoogle Scholar
  16. 16.
    Banovac, K., Lj. Bzik, D. Tislaric and M. Sekso, Conversion of thyroxine to triiodothyronine and reverse triiodothyronine in human placenta and fetal membranes, Hormone Res. 12: 253 (1980).PubMedCrossRefGoogle Scholar
  17. 17.
    Kaplan, M.M. and E. A. Shaw, Type II iodothyronine 5’deiodination by human and rat placenta in vitro, J. Clin. Endocrinol. Met. 59: 253 (1984).CrossRefGoogle Scholar
  18. 18.
    Weiss, R. M. and C. R. Noback, The effects of thyroxine and thiouracil on the time of appearance of ossification centers of rat fetuses, Endocrinology 45: 389 (1949).PubMedCrossRefGoogle Scholar
  19. 19.
    Porterfield, S. P. and C. E. Hendrich, The effects of growth hormone treatment on thyroid-deficient pregnant rats on maternal and fetal carbohydrate metabolism, Endocrinology 99: 786 (1976)PubMedCrossRefGoogle Scholar
  20. 20.
    Porterfield, S. P. and C. E. Hendrich, Alterations of serum thyroxine, triiodothyronine, and thyrotropin in the progeny of hypothyroid rats, Endocrinology 108: 1060 (1981)PubMedCrossRefGoogle Scholar
  21. 21.
    Hubank, M., M. Ballabio, A. Sinha, D. Gullo, S. Bidey, A. Bashir and R Ekins, Long term effects of maternal thyroidectomy on the development of the central nervous system of the progeny in the rat, Annales d’Endocrinologie 47: 48, (Abstract 79) (1986).Google Scholar
  22. 22.
    Bonet, B. and E. Herrera, Different response to maternal hypothyroidism during the first and second half of gestation in the rat, Endocrinology 122: 450 (1988)PubMedCrossRefGoogle Scholar
  23. 23.
    Pérez-Castillo, A., J. Bernal, B. Ferreiro and T. Pans, The early ontogenesis of thyroid hormone receptor in the rat fetus, Endocrinology 117: 2457 (1985).PubMedCrossRefGoogle Scholar
  24. 24.
    Luo,M. and J.H. Dussault, Immunocytochemical mapping of nuclear T3 receptors using a monoclonal antibody in the developing and adult brain, in:“Iodine in Neurodevelopment”, R. Delong and J. Robbins, eds., Plenum Press, New York, (1988).Google Scholar
  25. 25.
    Thompson, C. C., C. Weinberger, R. Lebo and R. M. Evans, Identification of a novel thyroid hormone receptor expressed in the mammalian central nervous system, Science 237: 1610 (1987)Google Scholar
  26. 26.
    Sap, J., A. Munoz, K. Damm, Y. Goldberg, J. Ghysdeal, A. Leutz, H. Beug and B. Vennstrom, The c-erb-A protein is a high affinity receptor for thyroid hormone. Nature 324: 635 (1986).PubMedCrossRefGoogle Scholar
  27. 27.
    Weinberger, C., C. C. Thompson, E. S. Ong, R. Lebo, D. J. Grunol and R. M. Evans, The c-erb-A gene encodes a thyroid hormone receptor, Nature 324: 641 (1986).PubMedCrossRefGoogle Scholar
  28. 28.
    Bernal, J. and F. Pekonen, Ontogenesis of the nuclear 3,5,3’-triiodothyronine receptor in the human fetal brain, Endocrinology 114: 677 (1984).PubMedCrossRefGoogle Scholar
  29. 29.
    Dobbing, J. and J. Sands, Timing of neuroblast multiplication in developing human brain, Nature 226: 639 (1970).PubMedCrossRefGoogle Scholar
  30. 30.
    Su, H. L., P. Ling, R. K. Yang and H.C. Chao, Ontogenesis of neclear T3 receptor in human fetal brain, in:“Iodine in Neurodevelopment”, R. Delong and J. Robbins, eds., Plenum Press, New York, (1988).Google Scholar
  31. 31.
    Karmarkar, M.G., D. Prabakaran, M. M. Godbole and M. M. S. Ahuja, Thyroid hormone contents and 5 & 5’ monodeiodinase activites in developping human cerebral cortex, in:“Iodine in Neurodevelopment”, R. Delong and J. Robbins, eds., Plenum Press, New York, (1988).Google Scholar
  32. 32.
    Weeke, J. and H. Orskov, Ultrasensitive radioimmunoassay for direct determination of free triiodothyronine concentration in serum, Scand. J. Clin. Lab. Invest. 35: 237 (1975)PubMedCrossRefGoogle Scholar
  33. 33.
    Obregbn, M.J., G. Morreale de Escobar and F, Escobar del Rey, Concentrations of triiodo-L-thyronine in the plasma and tissues of normal rats as determined by radioimmunoassay: Comparison with results obtained by an isotopic equilibrium technique, Endocrinology 103: 2154 (1978)CrossRefGoogle Scholar
  34. 34.
    Obregón, M.J., J. Mallol, F. Escobar del Rey and G. Morreale de Escobar, Presence of L-thyroxine and 3,5,3’triiodo-L-thyronine in tissues from thyroidectomized rats, Endocrinology 109: 908 (1981)PubMedCrossRefGoogle Scholar
  35. 35.
    Visser, T.J., J. L. Leonard, M. M. Kaplan and P. R. Larsen, Kinetic evidence suggesting two mechanisms for iodothyronine 5’-deiodination in rat cerebral cortex, Proc. Natl. Acad. Sci. 79: 5080 (1982).PubMedCrossRefGoogle Scholar
  36. 36.
    Morreale de Escobar, G., M. J. Obregbn, C. Ruiz de Ona and F. Escobar del Rey, Transfer of thyroxine from the mother to the rat fetus near term: effects on brain 3,5,3’-triiodothyronine deficiency, Endocrinology 122: 1521 (1988).CrossRefGoogle Scholar
  37. 37.
    Abrams, G.M. and P.R. Larsen, Triiodothyronine and thyroxine in the serum and thyroid glands of iodine-deficient rats, J Clin Invest 52: 2522 (1973).PubMedCrossRefGoogle Scholar
  38. 38.
    Iglesias, R., J.A. Fernandez, T. Mampel, M.J. Obregón and F. Villarroya, Iodothyronine 5’-deiodinase activity in rat brown adipose tissue during development, B. B. A. 923: 233 (1987).Google Scholar
  39. 39.
    McCann, U.D., E.A. Shaw and M.M. Kaplan, Iodothyronine deiodination reaction types in several rat tissues: Effects of age, thyroid status, and glucocorticoid treatment, Endocrinology 114: 1513 (1984).PubMedCrossRefGoogle Scholar
  40. 40.
    Segall-Blank, M., W.H. Douglas, R.L. Sanders and K.R. Hitchcock, Thyroxine metabolism in cultured cells derived from fetal rat lung, Pediatric Res. 17: 596 (1983).CrossRefGoogle Scholar
  41. 41.
    Nedergaard, J., E. Connolly and B. Cannon, Brown adipose tissue in the mammalian neonate, in: “Brown adipose tissue”, P. Trayhurn and D.G. Nicholls, eds, Edward Arnold, London, (1986), p 152.Google Scholar
  42. 42.
    Lean, M.E.J. and P.T. James, Brown adipose tissue in man, in: “Brown adipose tissue”, P. Trayhurn and D.G. Nicholls, eds, Edward Arnold, London, (1986), p 339.Google Scholar
  43. 43.
    Himms-Hagen, J., Brown adipose tissue and cold-acclimatation, ja: “Brown adipose tissue”, P. Trayhurn and D.G. Nicholls, eds, Edward Arnold, London, (1986), p 214.Google Scholar
  44. 44.
    Leonard, J. L., S. A. Mellen and P. R. Larsen, Thyroxine 5’-deiodinase activity in brown adipose tissue, Endocrinology 112: 1153 (1983).PubMedCrossRefGoogle Scholar
  45. 45.
    Silva, J. E. and P. R. Larsen, Interrelationships among thyroxine, growth hormone, and the sympathetic nervous system in the regulation of 5’-iodothyronine deiodinase in rat brown adipose tissue, J. Clin. Invest. 77: 1214 (1986).PubMedCrossRefGoogle Scholar
  46. 46.
    Silva, J. E. and P. R. Larsen, Adrenergic activation of triiodothyronine production in brown adipose tissue, Nature 305: 712 (1983).PubMedCrossRefGoogle Scholar
  47. 47.
    Silva, J. E. and P. R. Larsen, Potential of brown adipose tissue type II thyroxine 5’-deiodinase as a local and systemic source of triiodothyronine in rats, J. Clin. Invest. 76: 2296 (1985).PubMedCrossRefGoogle Scholar
  48. 48.
    Silva, J.E. and P. R. Larsen, Hormonal regulation of iodothyronine 5’-deiodinase in rat brown adipose tissue, Am. J. Physiol. 251: E639 (1986).PubMedGoogle Scholar
  49. 49.
    Bianco, A.C. and J. E. Silva, Nuclear 3,5,3`-triiodo thyronine (T3) in brown adipose tissue: Receptor occupancy and sources of T3 as determined by in vivo techniques, Endocrinology 120: 55 (1987)PubMedCrossRefGoogle Scholar
  50. 50.
    Escobar del Rey, F., R. Pastor, J. Mallol, and G. Morreale de Escobar, Effects of maternal iodine deficiency on the L-thyroxine and 3,5,3’-triiodothyronine contents of rat embryonic tissues before and after the onset of fetal thyroid function, Endocrinology 118: 1259 (1986).CrossRefGoogle Scholar
  51. 51.
    Obregon, M. J., R. Pitamber, A. Jacobsson, J. Nedergaard and B. Cannon, Euthyroid status is essential for the perinatal increase in thermogenin mRNA in brown adipose tissue of rat pups, B. B.R. C. 148: 9 (1987).Google Scholar
  52. 52.
    Hitchcock, K. R., Hormones and the lung. I. Thyroid hormones and glucocorticoids in lung development. Anat Rec 194: 15 (1979)PubMedCrossRefGoogle Scholar
  53. 53.
    Smith, R. M. Thyroid Hormones and Brain Development, in: “Fetal Brain Disorders” B. S. Hetzel, R. M. Smith, eds., Elsevier North Holland Publishing Co, Amsterdam (1981), p 149.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Maria Jesús Obregón
    • 1
  • Carmen Ruiz de Oña
    • 1
  • Francisco Escobar del Rey
    • 1
  • Gabriella Morreale de Escobar
    • 1
  1. 1.Unidad de Endocrinología Experimental, Instituto de Investigaciones BiomédicasC.S.I.C., Facultad de MedicinaMadridSpain

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