Skip to main content
Log in

Regional distribution of nuclear T3 receptors in rat brain and evidence for preferential localization in neurons1

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

We examined the distribution of nuclear T3 in mature rat brain with the aim of determining specific targets of thyroid hormones within this tissue. Saturation experiments, performed in 9 different structures of the brain and in 4 parts of the cortex, revealed the presence of a single class of binding sites with a mean Ka of 0.53 × 1010 M1. The highest concentrations of receptors were found in the amygdala (0.523 +0.025 ng T3/mg DNA, Mean ± SE) and the hippocampus (0.438 ± 0.071 ng T3/mg DNA) while the lowest were in the brain stem (0.058 ± 0.003 ngT3/mg DNA) and the cerebellum (0.079 ± 0.026 ngT3/ml DNA). The receptor was not uniformal-ly distributed within the cerebrel cortex, its concentration being relatively high in the central sections and intermediate in the remaining portions. The cell type distribution of the T3 receptor was studied by separating glial and neuronal nuclei on a discontinuous sucrose gradient. There was no detectable specific T3binding in the fraction of oligodendrocyte nuclei (~ 95% pure). Conversely, the neuron-enriched fraction (~ 60%) showed a significant increase in receptor concentration compared to total nuclei (35-40% neurons): 0.857 + 0.196 vs 0.511 + 0.095 ng T3/mg DNA (p < 0.01) in the cortex and 0.425 ± 0.018 vs 0.234 ± 0.24 ngT3/mg DNA (p < 0.01) in the forebrain. The absence of nuclear T3 receptors in oligodendrocytes may have important implications on the mechanism of action of thyroid hormone in myelination.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Grave G.D. Thyroid hormones and brain development. Raven Press, New York, 1977.

    Google Scholar 

  2. Weiner H. Hyperthyroidism. Emotions and. mentation. In: Werner S.C., Ingbar S.H. (Eds.), The thyroid. A functional and clinical text, ed 4. Harper and Row, Hagerstown, 1978, 753.

    Google Scholar 

  3. Weiner H. Hypothyroidism. Emotions and mentation. In: Werner S.C., Ingbar S.H., (Eds.), The thyroid. A functional and clinical text, ed 4. Harper and Row, Hargestown, 1978, p. 911.

    Google Scholar 

  4. Whybrow P.C., Prange A.J. A hypothesis of thyroid -catecholamine- receptor interaction. Its relevance to affective illness. Arch. Gen. Psychiatry 38:106, 1981.

    Article  PubMed  CAS  Google Scholar 

  5. Gross G., Brodde O.E., Schumann H.J. Effects of thyroid hormone deficiency on pre- and postsynaptic noradrenergic mechanisms in the rat cerebral cortex. Arch. Int. Pharmacodyn. Ther. 244: 219, 1981.

    Google Scholar 

  6. Gross G., Brodde O.E., Schumann H.J. Regulation of μ 1 -adrenoceptors in the cerebral cortex of the rat by thyroid hormones. Naunyn-Schmiedebergs. Arch. Pharmacol. 316: 45, 1981.

    Article  PubMed  CAS  Google Scholar 

  7. Ruiz-Marcos A., Sanchez-Toscano F., Escobar del Rey F., de Escobar G.M. Reversible morphological alterations of cortical neurons in juvenile and adult hypothyroidism in the rat. Brain Res. 185:91, 1980.

    Article  PubMed  CAS  Google Scholar 

  8. Walker P., Weichsel M.E., Fisher D.A., Guo S.M., Fisher D.A. Thyroxine increases nerve growth factor concentration in adult mouse brain. Science 204: 427, 1979.

    Article  PubMed  CAS  Google Scholar 

  9. Drozdz M., Kucharz E., Kozlowski A. Studies on 5’nucleotidase activity in blood serum, tissues and liver mitochondrial fraction of normal, hypo-and hyperthyroid rats. Endocrinology 65: 328, 1975.

    CAS  Google Scholar 

  10. Pinto J., Rivlin R.S. Regulation of formation of covalently bound flavins in liver and cerebrum by thyroid hormones. Arch. Biochem. Biophys. 194: 313, 1979.

    Article  PubMed  CAS  Google Scholar 

  11. Schwartz H.L., Oppenheimer J.H. Nuclear triiodothyronine receptor sites in brain: probable identity with hepatic receptors and regional distribution. Endocrinology 103: 267, 1978.

    Article  PubMed  CAS  Google Scholar 

  12. Eberhardt N.L., Valcana T., Timiras P.S. Triiodothyronine nuclear receptors: an in vitro comparison of the binding of triiodothyronine to nuclei of adult rat liver, cerebral hemisphere, and anterior pituitary. Endocrinology 102: 556, 1978.

    Article  PubMed  CAS  Google Scholar 

  13. Schwartz H.L., Oppenheimer J.H. Ontogenesis of 3,5,3′-triiodothyronine receptor in neonatal rat brain: dissociation between receptor concentration and stimulation of oxygen consumption by 3,5,3′-triiodothyronine. Endocrinology 103: 943, 1978.

    Article  PubMed  CAS  Google Scholar 

  14. Coulombe P., Ruel J., Dussault J.H. Récepteurs nucléaires de la T3 dans le cerveau et le cervelet du rat au cours du développement. Union Med. Can. 110:1, 1981.

    Google Scholar 

  15. Oppenheimer J.H. Thyroid hormone action at the cellular level. Science 203: 971, 1979.

    Article  PubMed  CAS  Google Scholar 

  16. Samuels H.H. In vitro studies on thyroid hormone receptors. In: O’Malley B.W., Birnhaumer L (Eds.), Receptors and hormone action. Academic Press, New York, 1977, vol. 3, p. 35.

    Google Scholar 

  17. Crantz F.R., Silva J.E., Larsen P.R. An analysis of the sources and quantity of 3,5,3′-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum. Endocrinology 110: 367, 1982.

    Article  PubMed  CAS  Google Scholar 

  18. Dratman M.B., Futaesaku Y., Crutchfield F.L., Berman N., Payne B., Sar M., Stumpf W.E. lodine-125-labeled triiodothyronine in rat brain: evidence for localization in discrete neural systems. Science 215: 309, 1982.

    Article  PubMed  CAS  Google Scholar 

  19. Thompson R.J. Studies on RNA synthesis in two populations of nuclei from the mammalian cerebral cortex. J. Neurochem. 21:19, 1973.

    Article  PubMed  CAS  Google Scholar 

  20. Las M.S., Surks M.I. Dissociation of serum triidothyronine concentration and hepatic nuclear triiodothyronine-binding capacity in streptozocin-induced diabetic rats. Endocrinology 109:1259, 1981.

    Article  PubMed  CAS  Google Scholar 

  21. Bernal J., DeGroot L.J. Thyroid hormone receptors: release of receptor to the medium during in vitro incubation of isolated rat liver nuclei. Endocrinology 100: 648, 1977.

    Article  PubMed  CAS  Google Scholar 

  22. Keightley D.D., Cressie M.A.C. The Woolf plot is more reliable than the Scatchard plot in analysing data from hormone receptor assays. J. Steroid Biochem. 13:1317, 1980.

    Article  PubMed  CAS  Google Scholar 

  23. Erwin B.G., Stoscheck C.M., Florini J.R. A rapid f luorometric method for the estimation of DNA in cultured cells. Anal. Biochem. 110: 291, 1981.

    Article  PubMed  CAS  Google Scholar 

  24. Kaplan M.M., McCann U.D., Yaskoski K.A., Larsen P.R., Leonard J.L Anatomical distribution of phenolic and tyrosyl ring iodo-thyronine deiodinase in the nervous system of normal and hypothyroid rats. Endocrinology 109: 397, 1981.

    Article  PubMed  CAS  Google Scholar 

  25. Legrand J. Morphogenetic action of thyroid hormones. Trends Neurosci. 2: 234, 1979.

    Article  Google Scholar 

  26. Jacobson M. Developmental neurobiology, ed 2. Plenum Press, New York, 1978.

    Book  Google Scholar 

  27. Balazs R., Brooksbank W.L., Davison A.N., Eayrs J.T., Wilson D.A. The effect of neonatal thyroidectomy on myelination in the rat brain. Brain Res. 15:219, 1969.

    Article  PubMed  CAS  Google Scholar 

  28. Freundl K., Van Wynsberghe D.M. The effects of thyroid hormones on myelination in the developing rat brain. Biol. Neonate 33: 217, 1978.

    Article  PubMed  CAS  Google Scholar 

  29. Bray G.M., Rasminsky M., Aguayo A.J. Interactions between axons and their sheath cells. Ann. Rev. Neurosci. 4:127, 1981.

    Article  PubMed  CAS  Google Scholar 

  30. Silva J.E., Matthews P.S. Production rates and turnover of T3 in rat developing cerebral cortex and cerebellum responses to hypothyroidism. J. Clin. Invest. 64:1035, 1984.

    Article  Google Scholar 

  31. Ruel J., Faure R., Dussault J.H. Nuclear T3 receptors in rat brain: differences in anatomical distribution and absence in oligodendrocytes. Proceedings of the American Thyroid Association Meeting, Quebec City, September 1982.

    Google Scholar 

  32. Bemal J., Pekonen F. Ontogenesis of the nuclear T3 receptor in the human fetal brain. Endocrinology 114: 677, 1984.

    Article  Google Scholar 

  33. Haidar M.A., Dubé S., Sarkar P.K. Thyroid hormone receptors of developing chick brain are predominantly in the neurons. Biochem. Biophys. Res. Commun. 112: 221, 1983.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work is supported by MRC grant MT-5730. Received October 3, 1984; accepted May 20, 1985.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruel, J., Faure, R. & Dussault, J.H. Regional distribution of nuclear T3 receptors in rat brain and evidence for preferential localization in neurons1 . J Endocrinol Invest 8, 343–348 (1985). https://doi.org/10.1007/BF03348511

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03348511

Key-words

Navigation