Thyroid System Ontogeny in the Sheep: A Model for Precocial Mammalian Species

  • Delbert A. Fisher
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 299)


Human thyroid system ontogenesis can be divided into three phases which roughly parallel the three classic trimesters of pregnancy. These include the period of embryogenesis during the first trimester, a period of relative hypothalamic-pituitary quiescence during the mid-trimester of pregnancy, and a final phase of synchronized maturation of hypothalamic-pituitary control of TSH secretion, thyroid hormone secretion, and peripheral iodothyronine metabolism (1). These phases of thyroid ontogenesis occur, as well, in other mammals and have been investigated in considerable detail in two models, the developing rat and the fetal sheep (1). In both models thyroid system development generally resembles human thyroid ontogenesis. However, in the rat, an altricial species, the total period of thyroid development encompasses about 50 days (21 fetal days + 28 postnatal days) and delivery occurs at approximately the midpoint of development during the phase of relative system quiescence. In the sheep, a precocial species, the period of thyroid system maturation extends from conception to two weeks of postnatal age, about 165 days. Birth occurs at approximately 150 days gestation in this species.


Thyroid Hormone Brown Adipose Tissue Congenital Hypothyroidism Fetal Sheep Thyroid Hormone Action 
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 DA, Dussault JH, Sack J, Chopra IJ. Ontogenesis of hypothalamic-pituitary-thyroid function and metabolism in man, sheep and rat. Rec Prog Horm Res 33: 59–116 (1977).Google Scholar
  2. 2.
    Fisher DA, Polk DH. Development of the thyroid, Bailliere’s Clinical Endocrinology and Metabolism 3: 627–657 (1989).CrossRefGoogle Scholar
  3. 3.
    Morreale de Escobar G and Escobar dei Rey F. Brain damage and thyroid hormone, In: Burrow GN and Dussault JH, Eds, Neonatal Thyroid Screening, Raven Press, New York, pp 25–50 (1980).Google Scholar
  4. 4.
    Kaufman P. Functional anatomy of the non-primate placenta. Placenta, Suppl. 1, 13–28 (1981).Google Scholar
  5. 5.
    Ramsey EM. Functional anatomy of the primate placenta. Placenta, Suppl. 1, 29–42 (1981).Google Scholar
  6. 6.
    Roti E, Gnudi A, Braverman LE. The placental transport, synthesis and metabolism of hormones and drugs which affect thyroid function. Endocrine Rev 4: 131–149 (1983).CrossRefGoogle Scholar
  7. 7.
    Morreale de Escobar G, Calvo R, Obregon MJ, Escobar del Rey F. Contribution of maternal thyroxine to fetal thyroxine pools in normal rats near term. Endocrinology 126: 2765–2767, (1990).CrossRefGoogle Scholar
  8. 8.
    Vulsma T, Gons MH, DeVijlder JJJM. Maternal fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis. N Engl J Med 321: 13–16 (1989).PubMedCrossRefGoogle Scholar
  9. 9.
    Bachrach LK, Kudlow JE, Silverberg H, Kent G, Burrow GN. Treatment of ovine cretinism in utero with 3,5,dimethyl-3’-isopropyl-l-thyronine. Endocrinology 111: 132–135 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    Mano MT, Potter BJ, Belling GB, Martin DN, Gragg BG, Chavadej J, Hetzel BS. The effect of thyroxine, 3,5, dimethyl-3’-isopropyl-l-thyroxine and iodized oil on fetal brain development in the iodine-deficient sheep. Acta Endocrinologica 121: 7–15 (1989).PubMedGoogle Scholar
  11. 11.
    Wu SY, Fisher DA, Polk D, Chopra IJ. Maturation of thyroid hormone metabolism, In: Wu SY, Hershman JM, Eds, Thyroid Hormone Metabolism: Regulation and clinical implications, Blackwell Scientific, New York, in press.Google Scholar
  12. 12.
    Polk DH, Wu SY, Fisher DA. Serum thyroid hormone and tissue 5’ monodeiodinase activity in acutely thyroidectomized newborn lambs. Am J Physiol 21: E151 - E155 (1986).Google Scholar
  13. 13.
    Wu SY, Polk DH, Fisher DA. Biochemical and ontogenic characterization of T4 5’monodeiodinase in brown adipose tissue from fetal and newborn lambs. Endocrinology 118: 1334–1339 (1986).PubMedCrossRefGoogle Scholar
  14. 14.
    Polk DH, Wu SY, Wright C, Reviczky AL, Fisher DA. Ontogeny of thyroid hormone effect on tissue 5’monodeiodinase activity in fetal sheep. Am J Physiol 254: E337 - E341 (1988).PubMedGoogle Scholar
  15. 15.
    Wu SY, Merryfield ML, Polk DH, Fisher DA. Two pathways for thyroxine 5’monodeiodination in brown adipose tissue in fetal sheep: ontogenesis and divergent responses to hypothyroidism and T3 replacement. Endocrinology 126: 1950–1958 (1990).PubMedCrossRefGoogle Scholar
  16. 16.
    Ferreiro B, Bernal J, Morreale de Escobar G, Potter BJ. Preferential saturation of brain 3,5,3’ triiodothyronine receptor during development in fetal lambs. Endocrinology 122: 438–443 (1988).PubMedCrossRefGoogle Scholar
  17. 17.
    Fisher DA. Development of fetal thyroid system control, In: Delong GR, Robbins J, Condliffe PG, Eds, Iodine and the Brain, Plenum Publishing Inc., New York, pp 167–176 (1989).CrossRefGoogle Scholar
  18. 18.
    Roti E. Regulation of thyroid-stimulating hormone (TSH) secretion in the fetus and neonate. J Endocrinol Invest 11: 145–158 (1988).PubMedGoogle Scholar
  19. 19.
    Klein AH, Oddie TH, Fisher DA. Effect of parturition on serum iodothyronine concentrations in fetal sheep. Endocrinology 103: 1453–1457 (1978).PubMedCrossRefGoogle Scholar
  20. 20.
    Polk DH, Padbury JF, Callegari C, Newnham JP, Reviczky AL, Klein AH, Fisher DA. Effect of fetal thyroidectomy on newborn thermogenesis in lambs. Pediatr Res 21: 453–457 (1987).PubMedCrossRefGoogle Scholar
  21. 21.
    Klein AH, Reviczky A, Chou P, Padbury J, Fisher DA. Development of brown adipose tissue thermogenesis in the ovine fetus and newborn. Endocrinology 112: 1662–1666 (1983).PubMedCrossRefGoogle Scholar
  22. 22.
    Bianco AC, Silva JE. Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue. J Clin Invest 79: 295–300 (1987).PubMedCrossRefGoogle Scholar
  23. 23.
    Wu SY, Klein AH, Chopra IJ, Fisher DA. Alterations in tissue thyroxine 5’-monodeiodinating activity in the perinatal period. Endocrinology 103: 235–239 (1978).PubMedCrossRefGoogle Scholar
  24. 24.
    Klein AH, Oddie TH, Fisher DA. Iodothyronine kinetic studies in the newborn lamb. J Devel Physiol 2: 29–35 (1980).Google Scholar
  25. 25.
    Fisher DA and Polk DH. Maturation of thyroid hormone actions, In: Delange F, Fisher DA, Glinoer D, Eds, Research in Congenital Hypothyroidism, Plenum Publishing Inc., New York, pp 61–77 (1989).Google Scholar
  26. 26.
    Ferreiro B, Bernal J, Potter BJ. Ontogenesis of thyroid hormone receptor in foetal lambs. Acta Endocrinologica 116: 205–210 (1987).PubMedGoogle Scholar
  27. 27.
    Polk DH, Cheromcha D, Reviczky A, Fisher DA. Nuclear thyroid hormone receptors: ontogeny and thyroid hormone effects in sheep. Am J Physiol 256: E543 - E549 (1989).PubMedGoogle Scholar
  28. 28.
    Polk DH, Reviczky A, Lam RW and Fisher DA. Thyrotropin releasing hormone in the ovine fetus: ontogeny and effect of thyroid hormone. Am J Physiol: in press.Google Scholar
  29. 29.
    Hetzel BS, Mano MT. A review of experimental studies of iodine deficiency during fetal development. J Nutr 119: 145–151 (1989).PubMedGoogle Scholar
  30. 30.
    Erenberg A, Omori K, Menkes JH, Oh W, Fisher DA. Growth and development of the thyroidectomized ovine fetus. Pediatric Res 8: 783–789 (1974).CrossRefGoogle Scholar
  31. 31.
    Castro R, Polk DH, Lam RW, Leake RD, Fisher DA. Atrial natriuretic factor (ANF): effect of thyroidectomy on concentration in fetal sheep atria and ventricles. Pediatric Res 23: 274A (1988).Google Scholar
  32. 32.
    Breall JA, Rudolph AM, Heymann MA. Role of thyroid hormone in postnatal circulating and metabolic adjustments. J Clin Invest 743: 1418–1424 (1984).CrossRefGoogle Scholar
  33. 33.
    Padbury JF, Klein AH, Polk DH, Lam RW, Hobel CJ, Fisher DA. The effect of thyroid status on lung and heart beta adrenergic receptors in fetal and newborn sheep. Devel Pharmacol Therapeut 9: 44–53 (1986).Google Scholar
  34. 34.
    Cheromcha DP, Callegari CC, Reviczky A, Polk DH, Fisher DA. Ontogenesis of thyroid hormone receptor and post-receptor effects in fetal ovine liver. Clin Res 35: 232A (1987).Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

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

Personalised recommendations