Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas

Monique H. A. Kester, Raquel Martinez de Mena, Maria Jesus Obregon, Danijela Marinkovic, Allan Howatson, Theo J. Visser, Robert Hume, Gabriella Morreale de Escobar

    Research output: Contribution to journalArticle

    213 Citations (Scopus)

    Abstract

    Thyroid hormones are required for human brain development, but data on local regulation are limited. We describe the ontogenic changes in T4, T3, and rT3 and in the activities of the types I, II, and III iodothyronine deiodinases (D1, D2, and D3) in different brain regions in normal fetuses (13–20 wk postmenstrual age) and premature infants (24–42 wk postmenstrual age). D1 activity was undetectable. The developmental changes in the concentrations of the iodothyronines and D2 and D3 activities showed spatial and temporal specificity but with divergence in the cerebral cortex and cerebellum. T3 increased in the cortex between 13 and 20 wk to levels higher than adults, unexpected given the low circulating T3. Considerable D2 activity was found in the cortex, which correlated positively with T4 (r = 0.65). Cortex D3 activity was very low, as was D3 activity in germinal eminence and choroid plexus. In contrast, cerebellar T3 was very low and increased only after midgestation. Cerebellum D3 activities were the highest (64 fmol/min·mg) of the regions studied, decreasing after midgestation. Other regions with high D3 activities (midbrain, basal ganglia, brain stem, spinal cord, hippocampus) also had low T3 until D3 started decreasing after midgestation. D3 was correlated with T3 (r = –0.682) and rT3/T3 (r = 0.812) and rT3/T4 (r = 0.889). Our data support the hypothesis that T3 is required by the human cerebral cortex before midgestation, when mother is the only source of T4. D2 and D3 play important roles in the local bioavailability of T3. T3 is produced from T4 by D2, and D3 protects brain regions from excessive T3 until differentiation is required.
    Original languageEnglish
    Pages (from-to)3117-3128
    Number of pages12
    JournalJournal of Clinical Endocrinology & Metabolism
    Volume89
    Issue number7
    DOIs
    Publication statusPublished - Jul 2004

    Fingerprint

    Iodide Peroxidase
    Brain
    Cerebral Cortex
    Cerebellum
    Choroid Plexus
    Human Development
    Mesencephalon
    Basal Ganglia
    Thyroid Hormones
    Premature Infants
    Biological Availability
    Brain Stem
    Hippocampus
    Spinal Cord
    Fetus
    Mothers

    Keywords

    • Brain embryology
    • Infants
    • Premature metabolism
    • Premature metabolism
    • Thyroxine metabolism
    • Triiodothyronine metabolism
    • Triiodothyronine, reverse metabolism

    Cite this

    Kester, M. H. A., de Mena, R. M., Obregon, M. J., Marinkovic, D., Howatson, A., Visser, T. J., ... de Escobar, G. M. (2004). Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas. Journal of Clinical Endocrinology & Metabolism, 89(7), 3117-3128. https://doi.org/10.1210/jc.2003-031832
    Kester, Monique H. A. ; de Mena, Raquel Martinez ; Obregon, Maria Jesus ; Marinkovic, Danijela ; Howatson, Allan ; Visser, Theo J. ; Hume, Robert ; de Escobar, Gabriella Morreale. / Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas. In: Journal of Clinical Endocrinology & Metabolism. 2004 ; Vol. 89, No. 7. pp. 3117-3128.
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    abstract = "Thyroid hormones are required for human brain development, but data on local regulation are limited. We describe the ontogenic changes in T4, T3, and rT3 and in the activities of the types I, II, and III iodothyronine deiodinases (D1, D2, and D3) in different brain regions in normal fetuses (13–20 wk postmenstrual age) and premature infants (24–42 wk postmenstrual age). D1 activity was undetectable. The developmental changes in the concentrations of the iodothyronines and D2 and D3 activities showed spatial and temporal specificity but with divergence in the cerebral cortex and cerebellum. T3 increased in the cortex between 13 and 20 wk to levels higher than adults, unexpected given the low circulating T3. Considerable D2 activity was found in the cortex, which correlated positively with T4 (r = 0.65). Cortex D3 activity was very low, as was D3 activity in germinal eminence and choroid plexus. In contrast, cerebellar T3 was very low and increased only after midgestation. Cerebellum D3 activities were the highest (64 fmol/min·mg) of the regions studied, decreasing after midgestation. Other regions with high D3 activities (midbrain, basal ganglia, brain stem, spinal cord, hippocampus) also had low T3 until D3 started decreasing after midgestation. D3 was correlated with T3 (r = –0.682) and rT3/T3 (r = 0.812) and rT3/T4 (r = 0.889). Our data support the hypothesis that T3 is required by the human cerebral cortex before midgestation, when mother is the only source of T4. D2 and D3 play important roles in the local bioavailability of T3. T3 is produced from T4 by D2, and D3 protects brain regions from excessive T3 until differentiation is required.",
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    Kester, MHA, de Mena, RM, Obregon, MJ, Marinkovic, D, Howatson, A, Visser, TJ, Hume, R & de Escobar, GM 2004, 'Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas', Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 7, pp. 3117-3128. https://doi.org/10.1210/jc.2003-031832

    Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas. / Kester, Monique H. A.; de Mena, Raquel Martinez; Obregon, Maria Jesus; Marinkovic, Danijela; Howatson, Allan; Visser, Theo J.; Hume, Robert; de Escobar, Gabriella Morreale.

    In: Journal of Clinical Endocrinology & Metabolism, Vol. 89, No. 7, 07.2004, p. 3117-3128.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas

    AU - Kester, Monique H. A.

    AU - de Mena, Raquel Martinez

    AU - Obregon, Maria Jesus

    AU - Marinkovic, Danijela

    AU - Howatson, Allan

    AU - Visser, Theo J.

    AU - Hume, Robert

    AU - de Escobar, Gabriella Morreale

    N1 - dc.publisher: Endocrine Society dc.description.sponsorship: European Community Grant QLG-2000-00930 Netherlands Organization for Scientific Research Grant 903-40-204 Fondo de Investigacion Sanitaria RCMN (C03/08) from Inst de Salud Carlos III Chief Scientists Office Scottish Executive (K/MRS/50/C741) Tenovus Scotland/Leng Trust

    PY - 2004/7

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    N2 - Thyroid hormones are required for human brain development, but data on local regulation are limited. We describe the ontogenic changes in T4, T3, and rT3 and in the activities of the types I, II, and III iodothyronine deiodinases (D1, D2, and D3) in different brain regions in normal fetuses (13–20 wk postmenstrual age) and premature infants (24–42 wk postmenstrual age). D1 activity was undetectable. The developmental changes in the concentrations of the iodothyronines and D2 and D3 activities showed spatial and temporal specificity but with divergence in the cerebral cortex and cerebellum. T3 increased in the cortex between 13 and 20 wk to levels higher than adults, unexpected given the low circulating T3. Considerable D2 activity was found in the cortex, which correlated positively with T4 (r = 0.65). Cortex D3 activity was very low, as was D3 activity in germinal eminence and choroid plexus. In contrast, cerebellar T3 was very low and increased only after midgestation. Cerebellum D3 activities were the highest (64 fmol/min·mg) of the regions studied, decreasing after midgestation. Other regions with high D3 activities (midbrain, basal ganglia, brain stem, spinal cord, hippocampus) also had low T3 until D3 started decreasing after midgestation. D3 was correlated with T3 (r = –0.682) and rT3/T3 (r = 0.812) and rT3/T4 (r = 0.889). Our data support the hypothesis that T3 is required by the human cerebral cortex before midgestation, when mother is the only source of T4. D2 and D3 play important roles in the local bioavailability of T3. T3 is produced from T4 by D2, and D3 protects brain regions from excessive T3 until differentiation is required.

    AB - Thyroid hormones are required for human brain development, but data on local regulation are limited. We describe the ontogenic changes in T4, T3, and rT3 and in the activities of the types I, II, and III iodothyronine deiodinases (D1, D2, and D3) in different brain regions in normal fetuses (13–20 wk postmenstrual age) and premature infants (24–42 wk postmenstrual age). D1 activity was undetectable. The developmental changes in the concentrations of the iodothyronines and D2 and D3 activities showed spatial and temporal specificity but with divergence in the cerebral cortex and cerebellum. T3 increased in the cortex between 13 and 20 wk to levels higher than adults, unexpected given the low circulating T3. Considerable D2 activity was found in the cortex, which correlated positively with T4 (r = 0.65). Cortex D3 activity was very low, as was D3 activity in germinal eminence and choroid plexus. In contrast, cerebellar T3 was very low and increased only after midgestation. Cerebellum D3 activities were the highest (64 fmol/min·mg) of the regions studied, decreasing after midgestation. Other regions with high D3 activities (midbrain, basal ganglia, brain stem, spinal cord, hippocampus) also had low T3 until D3 started decreasing after midgestation. D3 was correlated with T3 (r = –0.682) and rT3/T3 (r = 0.812) and rT3/T4 (r = 0.889). Our data support the hypothesis that T3 is required by the human cerebral cortex before midgestation, when mother is the only source of T4. D2 and D3 play important roles in the local bioavailability of T3. T3 is produced from T4 by D2, and D3 protects brain regions from excessive T3 until differentiation is required.

    KW - Brain embryology

    KW - Infants

    KW - Premature metabolism

    KW - Premature metabolism

    KW - Thyroxine metabolism

    KW - Triiodothyronine metabolism

    KW - Triiodothyronine, reverse metabolism

    U2 - 10.1210/jc.2003-031832

    DO - 10.1210/jc.2003-031832

    M3 - Article

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    JO - Journal of Clinical Endocrinology and Metabolism

    JF - Journal of Clinical Endocrinology and Metabolism

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    IS - 7

    ER -