Development of Fetal Thyroid System Control

  • Delbert A. Fisher


The hypothalamic-pituitary-thyroid system in the fetus is comprised of a complex of hypothalamic centers, anterior pituitary thyrotroph cells, thyroid follicular cells, and peripheral tissues which metabolize and respond to thyroid hormones. Embryogenesis of the hypothalamus and of the pituitary and thyroid glands is largely completed by 12 weeks of gestation in the human fetus. Hypothalamic histogenesis and differentiation and continued growth and functional maturation of the pituitary and thyroid glands proceed into the neonatal period (1). Studies of thyroid system maturation have been conducted in many species, but most detailed data have been developed in the sheep and rat models. The period of thyroid system development in man, a precocial species, extends to one month of postnatal life (some 44 weeks). In the sheep (also a precocial species), comparable thyroid system maturation encompasses 150 days of intrauterine gestation plus two weeks of postnatal life (165 days total). In the rat (an altricial species) thyroid system development requires some 50 days (21 fetal days + 28 postnatal days). Relative thyroid system maturation in these species is quite comparable and thyroid control matures during the latter half of the period of ontogenesis. Thus, the third trimester fetal sheep and neonatal lamb and the neonatal rat have served as useful models for the study of thyroid control maturation. The following discussion of the development of various aspects of control of thyroid hormone production will review data in the three species normalized as relative development time to facilitate species comparisons.


Thyrotropin Release Hormone Human Fetus Thyroid Hormone Secretion Thyroid System Neonatal Lamb 
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., Dussault, J.H., Sack, J. and Chopra, I.J. (1977) Ontogenesis of hypothalamic-pituitary-thyroid function and metabolism in man, sheep, and rat. Rec Prog Horm Res 33: 59Google Scholar
  2. 2.
    Gershengorn, M.C. (1986) Thyrotropin releasing hormone stimulation of pituitary hormone secretion. Ann Rev Physiol 48: 515CrossRefGoogle Scholar
  3. 3.
    Lippman, S.S., Amr, S. and Weintraub, B. (1986) Discordant effects of thyrotropin (TSH)-releasing hormone on pre- and postranslational regulation of TSH biosynthesis in rat pituitary. Endocrinology 119: 343PubMedCrossRefGoogle Scholar
  4. 4.
    Morley, J.E. (1981) Neuroendocrine control of thyrotropin secretion. Endocrine Rev 2: 396CrossRefGoogle Scholar
  5. 5.
    Hinkle, P.M. and Goh, K.B.C. (1982) Regulation of thyrotropin releasing hormone receptors and responses by l-triiodothyronine in dispersed rat pituitary cell cultures. Endocrinology 110: 1725PubMedCrossRefGoogle Scholar
  6. 6.
    Kaplan, M.M. (1983) Metabolism of thyroid hormones. In: Congenital Hypothyroidism ( Dussault JH and Walker P, Eds), Marcel Dekker Inc., New York, pp 11 – 35Google Scholar
  7. 7.
    Banerji, A. and Prasad, C. (1982) The postnatal development of the pituitary thyrotropin releasing hormone receptor in male and female rats. Endocrinology 110: 663PubMedCrossRefGoogle Scholar
  8. 8.
    Delange, F., Dalhem, A., Bourdoux, P., Lagasse, R., Glinoer, D., Fisher, D.A., Walfish, P.G. and Ermans, A.M. (1984) Increased risk of primary hypothyroidism in preterm infants. J Pediatr 105: 462PubMedCrossRefGoogle Scholar
  9. 9.
    Klein, A.H. and Fisher, D.A. (1980) Thyrotropin releasing hormone stimulated pituitary and thyroid gland responsiveness and 3, 5, 3’-triiodothyronine suppression in fetal and neonatal lambs. Endocrinology 106:697PubMedCrossRefGoogle Scholar
  10. 10.
    Walker, P., Coulombe, P. and Dussault, J.H. (1980) Effects of triiodothyronine on thyrtropin releasing hormone induced thyrotropin release in the neonatal rat. Endocrinology 107: 1731PubMedCrossRefGoogle Scholar
  11. 11.
    Gyves, P.W., Gesundheit, N., Taylor, T., Butler, J.B. and Weintraub, B.D. (1987) Changes in thyrotropin (TSH) carbohydrate structure and response by concanavalin-A chromatography. Endocrinology 121: 133PubMedCrossRefGoogle Scholar
  12. 12.
    Cheron, R.G., Kaplan, M.M. and Larsen, P.R. (1980) Divergent changes in thyroxine 5’ monodeiodination in rat pituitary and liver during maturation. Endocrinology 106: 1405PubMedCrossRefGoogle Scholar
  13. 13.
    Segall-Blank, M., Connolly, J.L. and Ingbar, S.H. (1982) Comparative studies of the metabolism of thyroxine on the pituitaries of pregnant sheep and their fetuses. Endocrinology 111: 1996PubMedCrossRefGoogle Scholar
  14. 14.
    Coulombe, P., Ruel, J., Favre, R. and Dusssault, J.H. (1983) Pituitary nuclear triiodothyronine receptors during development in the rat. Am J Physiol: Endocrinol Metab 8: E81Google Scholar
  15. 15.
    Price, D.J. and Sherwin, J.R. (1986) Autoregulation of iodide transport in the rabbit: absence of autoregulation in fetal tissue and comparison of maternal and fetal thyroid iodination products. Endocrinology 119: 2547PubMedCrossRefGoogle Scholar
  16. 16.
    Castaign, H., Fournet, J.P., Leger, F.A., Keisgen, F., Piette, C., Dupard, M.C. and Savoie, J.C. (1979) Thyroid of the newborn and postnatal iodine overload. Arch Fr Pediatr 36: 356Google Scholar
  17. 17.
    Theodoropoulos, T., Fang, S.L., Prosky, J. and Vagenakis, A.G. (1979) Iodide induced hypothyroidism: a potential hazard during perinatal life. Science 205: 502PubMedCrossRefGoogle Scholar
  18. 18.
    Sherwin, J.R. and Price, D.J. (1986) Autoregulation of thyroid iodide transport: evidence for the mediation of protein synthesis in iodide-induced suppression of iodide transport. Endocrinology 119: 2553PubMedCrossRefGoogle Scholar
  19. 19.
    Oliver, C., Giraud, P. and Conte-Devolx, B. (1982) Influence of endogenous somatostatin on growth hormone and thyrotropin secretion in neonatal rats. Endocrinology 110: 1018PubMedCrossRefGoogle Scholar
  20. 20.
    Polk, D.H., Reviczky, A.L., Lam, R.W. and Fisher, D.A. (1988) Thyrotropin releasing hormone: effect of thyroid status on tissue concentrations in fetal sheep. Clin Res 36: 203AGoogle Scholar
  21. 21.
    Engler, D., Scanlon, M.F. and Jackson, I.M.D. (1981) Thyrotropin releasing hormone in the systemic circulation of the neonatal rat is derived from the pancreas and other extraneural tissues. J Clin Invest 67: 800PubMedCrossRefGoogle Scholar
  22. 22.
    Strbak, V. and Greer, M.A. (1979) Acute effects of hypothalamic ablation on plasma thyrotropin and prolactin concentrations in the suckling rat: Evidence that early postnatal pituitary-thyroid regulation is independent of hypothalamic control. Endocrinology 105: 488.PubMedCrossRefGoogle Scholar
  23. 23.
    Strbak, V. and Greer, M.A. (1981) Thyrotropin secretory response to thyrotropin releasing hormone in the hypothyroid perinatal rat: Further evidence of thyrotroph independence of the hypothalamus during early ontogenesis. Endocrinology 108: 1403PubMedCrossRefGoogle Scholar
  24. 24.
    Theodoropoulos, T., Braverman, L.E. and Vagenakis, A.G. (1979) Thyrotropin releasing hormone is not required for thyrotropin secretion in the perinatal rat. J Clin Invest 63: 588PubMedCrossRefGoogle Scholar
  25. 25.
    Oliver, C., Giraud, P., Lissitzky, J.C., Conte-Devolx, B. and Gillioz, P. (1981) Influence of thyrotropin releasing hormone on the secretion of thyrotropin in neonatal rats. Endocrinology 108: 179.PubMedCrossRefGoogle Scholar
  26. 26.
    Fisher, D.A. and Klein, A.H. (1981) Thyroid development and disorders of thyroid function in the newborn. New Engl J Med 304: 702PubMedCrossRefGoogle Scholar
  27. 27.
    Fraser, M., Gunn, T.R., Butler, J.H., Johnston, B.M. and Gluckman, P.D. (1985) Circulating thyrotropin in the ovine fetus: evidence for pulsatile release and the effect of hypothermia in utero. Pediatr Res 19: 208PubMedCrossRefGoogle Scholar
  28. 28.
    Fisher, D.A. and Odell, W.D. (1969) Acute release of thyrotropin in the newborn. J Clin Invest 48: 1670.PubMedCrossRefGoogle Scholar
  29. 29.
    Frankel, S. and Lange, G. (1980) Maturation of hypothalamic-pituitary thyroid response in the rat to acute cold. Am J Physiol (Endocrinol Metab)2: E223Google Scholar
  30. 30.
    Theodoropoulos, T., Braverman, L.E. and Vagenakis, A.G. (1979) Circulating immunoreactive TRH in the neonatal rat. Dissociation between TRH release and TSH response following cold exposure. Endocrine Soc., Abstr. 427Google Scholar
  31. 31.
    Sack, J., Fisher, D.A., Grawer, L.A., Lam, R.W. and Wang, C.C. (1977) The response of newborn sheep to TRH with and without somatostatin. Endocrinology 100: 1533PubMedCrossRefGoogle Scholar
  32. 32.
    Becu, D. and Libertun, C. (1982) Comparative maturation of the regulation of prolactin and thyrotropin by serotonin and thyrotropin-releasing-hormone in male and female rats. Endocrinology 110: 1879PubMedCrossRefGoogle Scholar
  33. 33.
    Roti, E., Robuschi, G., Emanuele, R., D’Amato, L., Gnudi, A., Fatone, M., Benassi, L., Foscolo, M.S., Gualerzi, C., and Braverman, L.E. (1983) Failure of metoclopramide to affect thyrotropin concentration in the term human fetus. J Clin Endocrinol Metab 56: 1071PubMedCrossRefGoogle Scholar
  34. 34.
    Harris, A.R.C., Fang, S.L., Prosky, J., Braverman, L.E. and Vagenakis, A.G. (1978) Decreased outer ring monodeiodination of thyroxine and reverse triiodothyronine in the fetal and neonatal rat. Endocrinology 103: 2216PubMedCrossRefGoogle Scholar
  35. 35.
    Klein, A.H., Oddie, T.H., Parslow, M., Foley, T.P., Jr. and Fisher, D.A. (1982) Development changes in pituitary thyroid function in the human fetus and newborn. Early Human Devel 6: 321CrossRefGoogle Scholar
  36. 36.
    Hadeed, A.J., Asay, L.D., Klein, A.H. and Fisher, D.A. (1981) Significance of transient postnatal hypohthyroxinemia in premature infants with and without RDS. Pediatrics 68: 494PubMedGoogle Scholar
  37. 37.
    Koivusalo, F., (1981) Evidence of thyrotropin releasing hormone activity in autopsy pancreata from newborns. J Clin Endocrinol Metab 53: 734PubMedCrossRefGoogle Scholar
  38. 38.
    Leduque, P., Aratan-Spire, S., Czernichow, P. and Dubois, P.M. (1986) Ontogenesis of thyrotropin releasing hormone in human fetal pancreas. J Clin Invest 78: 1028PubMedCrossRefGoogle Scholar
  39. 39.
    Perelman, A.H., Klein, A.H. and Fisher, D.A.: Cord blood thyrotropin releasing hormone. Clin Res. 29:111A (Abstract).Google Scholar
  40. 40.
    Segerson, T.P., Kauer, J., Wolfe, H.C., Mobtaker, H., Wu, P., Jackson, I.M.D. and Lechan, R.M. (1987) Thyroid hormone regulates TRH biosynthesis in the paraventricular nucleus of the rat hypothalamus. Science 238: 78PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Delbert A. Fisher
    • 1
  1. 1.Department of PediatricsHarbor-UCLA Medical CenterTorranceUSA

Personalised recommendations