Skip to main content
Erschienen in: Metabolic Brain Disease 2/2018

03.08.2017 | Original Article

Expression of thyroid-stimulating hormone receptors and thyroglobulin in limbic regions in the adult human brain

verfasst von: Meleshni Naicker, Strinivasen Naidoo

Erschienen in: Metabolic Brain Disease | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Expression of the human thyroid-specific proteins, thyroid-stimulating hormone receptor (TSH-R) and thyroglobulin (TG) in non-thyroid tissue is well-documented. TSH-R has been identified in the heart, kidney, bone, pituitary, adipose tissue, skin and astrocyte cultures. TG has been identified in the skin, thymus and kidney. However, none of those previous studies had identified TSH-R or TG in specific human brain regions. Previously, a pilot study conducted by our group on normal adult human brain demonstrated TSH-R and TG in cortical neurons and cerebral vasculature, respectively, within various brain areas. In the present study, we extend this investigation of thyroid proteins specifically in limbic regions of normal human brain. Forensic human samples of amygdalae, cingulate gyrii, frontal cortices, hippocampii, hypothalamii, and thalamii were obtained from five individuals who had died of causes unrelated to head injury and had no evidence of brain disease or psychological abnormality. Tissues were probed with commercial polyclonal antibodies against human TSH-R and TG which resulted in the significant demonstration of neuronal TSH-R in all limbic regions examined. Other novel results demonstrated TG in vascular smooth muscle of all limbic regions and in some neurons. Finding thyroid proteins in limbic areas of the human brain is unique, and this study demonstrates that cerebro-limbic localisation of thyroid proteins may have potential roles in neuro-psycho-pharmacology.
Literatur
Zurück zum Zitat Ai J, Leonardt JM, Heymann WR (2003) Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations. J Am Acad Dermatol 48:641–662CrossRefPubMed Ai J, Leonardt JM, Heymann WR (2003) Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations. J Am Acad Dermatol 48:641–662CrossRefPubMed
Zurück zum Zitat Berer K, Wekerle H, Krishnamoorthy G (2011) B cells in spontaneous autoimmune diseases of the central nervous system. Mol Immunol 48:1332–1337CrossRefPubMed Berer K, Wekerle H, Krishnamoorthy G (2011) B cells in spontaneous autoimmune diseases of the central nervous system. Mol Immunol 48:1332–1337CrossRefPubMed
Zurück zum Zitat Bockmann J, Winter C, Wittkowski W, Kreutz MR, Bockers TM (1997) Cloning and expression of a brain-derived TSH-receptor. Biochem Biophys Res Commun 238:173–178CrossRefPubMed Bockmann J, Winter C, Wittkowski W, Kreutz MR, Bockers TM (1997) Cloning and expression of a brain-derived TSH-receptor. Biochem Biophys Res Commun 238:173–178CrossRefPubMed
Zurück zum Zitat Bodo E, Kromminga A, Biro T, Borbiro I, Gaspar E, Zmijewski MA, van Beek N, Langbein L, Slominski AT, Paur R (2009) Human female hair follicles are a direct, nonclassical target for thyroid-stimulating hormone. J Invest Dermatol 129:1126–1139CrossRefPubMed Bodo E, Kromminga A, Biro T, Borbiro I, Gaspar E, Zmijewski MA, van Beek N, Langbein L, Slominski AT, Paur R (2009) Human female hair follicles are a direct, nonclassical target for thyroid-stimulating hormone. J Invest Dermatol 129:1126–1139CrossRefPubMed
Zurück zum Zitat Bolton SJ, Anthony DC, Perry VH (1998) Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 86:1245–1257CrossRefPubMed Bolton SJ, Anthony DC, Perry VH (1998) Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 86:1245–1257CrossRefPubMed
Zurück zum Zitat Chabaud O, Lissitzky S (1977) Thyrotropin-specfic binding to human peripheral blood monocytes and polymorphonuclear leukocytes. Mol Cell Endocrinol 7:79–87CrossRefPubMed Chabaud O, Lissitzky S (1977) Thyrotropin-specfic binding to human peripheral blood monocytes and polymorphonuclear leukocytes. Mol Cell Endocrinol 7:79–87CrossRefPubMed
Zurück zum Zitat Cianfarani F, Baldini E, Cavalli A, Marchioni E, Lembo L, Teson M, Persecjino S, Zambruno G, Ulisse S, Odorisio T, D’Armiento M (2010) TSH receptor and thyroid-specific gene expression in human skin. J Invest Dermatol 130:93–101CrossRefPubMed Cianfarani F, Baldini E, Cavalli A, Marchioni E, Lembo L, Teson M, Persecjino S, Zambruno G, Ulisse S, Odorisio T, D’Armiento M (2010) TSH receptor and thyroid-specific gene expression in human skin. J Invest Dermatol 130:93–101CrossRefPubMed
Zurück zum Zitat Clement K, Viguerie N, Diehn M, Alizadeh A, Barbe P, Thalamas C (2002) In vivo regulation of human skeletal muscle gene expression by thyroid hormone. Genome Res 12:281–291CrossRefPubMedPubMedCentral Clement K, Viguerie N, Diehn M, Alizadeh A, Barbe P, Thalamas C (2002) In vivo regulation of human skeletal muscle gene expression by thyroid hormone. Genome Res 12:281–291CrossRefPubMedPubMedCentral
Zurück zum Zitat Crisanti P, Omri B, Hughes E, Meduri G, Hery C, Clauser E, Jacquemin C, Saunier B (2001) The expression of thyrotropin receptor in the brain. Endocrinology 142:812–822CrossRefPubMed Crisanti P, Omri B, Hughes E, Meduri G, Hery C, Clauser E, Jacquemin C, Saunier B (2001) The expression of thyrotropin receptor in the brain. Endocrinology 142:812–822CrossRefPubMed
Zurück zum Zitat Drvota V, Janson A, Norman C, Sylven C (1995) Evidence for the presence of functional thyrotropin receptor in cardiac muscle. Biochem Biophys Res Commun 211:426–431CrossRefPubMed Drvota V, Janson A, Norman C, Sylven C (1995) Evidence for the presence of functional thyrotropin receptor in cardiac muscle. Biochem Biophys Res Commun 211:426–431CrossRefPubMed
Zurück zum Zitat Endo T, Ohta K, Haraguchi K, Onaya T (1995) Cloning and functional expression of a thyrotropin receptor cDNA from rat cells. J Biol Chem 270:10833–10837CrossRefPubMed Endo T, Ohta K, Haraguchi K, Onaya T (1995) Cloning and functional expression of a thyrotropin receptor cDNA from rat cells. J Biol Chem 270:10833–10837CrossRefPubMed
Zurück zum Zitat Freitas BCG, Gereben B, Castillo M, Kallo I, Zeold A, Egri P et al (2010) Paracrine signalling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells. J Clin Invest 120:2206–2217CrossRefPubMedPubMedCentral Freitas BCG, Gereben B, Castillo M, Kallo I, Zeold A, Egri P et al (2010) Paracrine signalling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells. J Clin Invest 120:2206–2217CrossRefPubMedPubMedCentral
Zurück zum Zitat Guyton AC, Hall JE (2000) Textbook of medical physiology, tenth edn. Elsevier, Philadelphia Guyton AC, Hall JE (2000) Textbook of medical physiology, tenth edn. Elsevier, Philadelphia
Zurück zum Zitat Inoue M, Tawata M, Yokomori N, Endo T, Onaya T (1998) Expression of thyrotropin receptor on clonal osteoblast-like rat osteosarcoma cells. Thyroid 8:1059–1064CrossRefPubMed Inoue M, Tawata M, Yokomori N, Endo T, Onaya T (1998) Expression of thyrotropin receptor on clonal osteoblast-like rat osteosarcoma cells. Thyroid 8:1059–1064CrossRefPubMed
Zurück zum Zitat Kumar RS, Ijiri S, Kight K, Swanson P, Dittmann A (2000) Cloning and functional expression of a thyrotropin receptor from the gonads of a vertebrate (bony fish): potential thyroid-independent role for thyrotropin in reproduction. Mol Cell Endocrinol 167:1–9CrossRefPubMed Kumar RS, Ijiri S, Kight K, Swanson P, Dittmann A (2000) Cloning and functional expression of a thyrotropin receptor from the gonads of a vertebrate (bony fish): potential thyroid-independent role for thyrotropin in reproduction. Mol Cell Endocrinol 167:1–9CrossRefPubMed
Zurück zum Zitat Lou J, Chofflon M, Juillard C, Donati Y, Mili N, Siegrisy CA, Grau GE (1997) Brain microvascular endothelial cells and leukocytes derived from patients with multiple sclerosis exhibit increased adhesion capacity. Neuroreport 8:629–633CrossRefPubMed Lou J, Chofflon M, Juillard C, Donati Y, Mili N, Siegrisy CA, Grau GE (1997) Brain microvascular endothelial cells and leukocytes derived from patients with multiple sclerosis exhibit increased adhesion capacity. Neuroreport 8:629–633CrossRefPubMed
Zurück zum Zitat Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C (2002) The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 202:13–23CrossRefPubMed Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C (2002) The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 202:13–23CrossRefPubMed
Zurück zum Zitat Moodley K, Botha J, Raidoo DM, Naidoo S (2011) Immuno-localisation of anti-thyroid antibodies in adult human cerebral cortex. J Neurol Sci 302:114–117CrossRefPubMed Moodley K, Botha J, Raidoo DM, Naidoo S (2011) Immuno-localisation of anti-thyroid antibodies in adult human cerebral cortex. J Neurol Sci 302:114–117CrossRefPubMed
Zurück zum Zitat Murakami M, Hosoi Y, Negishi T, Kamiya Y, Miyashita K, Yamada M, Iriuchijima T, Yokoo K, Yoshida I, Tsushima Y, Mori M (1996) Thymic hyperplasia in patients with graves’ disease. Identification of thyrotropin receptors in human thymus. J Clin Invest 98:2228–2234CrossRefPubMedPubMedCentral Murakami M, Hosoi Y, Negishi T, Kamiya Y, Miyashita K, Yamada M, Iriuchijima T, Yokoo K, Yoshida I, Tsushima Y, Mori M (1996) Thymic hyperplasia in patients with graves’ disease. Identification of thyrotropin receptors in human thymus. J Clin Invest 98:2228–2234CrossRefPubMedPubMedCentral
Zurück zum Zitat Nwoye L, Mommaerts WF, Simpson DR, Seradarian K, Marusich M (1982) Evidence for a direct action of thyroid hormone in specifying muscle properties. Am J Phys 242:R401–R408 Nwoye L, Mommaerts WF, Simpson DR, Seradarian K, Marusich M (1982) Evidence for a direct action of thyroid hormone in specifying muscle properties. Am J Phys 242:R401–R408
Zurück zum Zitat Ojamaa K, Klemperer JD, Klein I (1996) Acute effects of thyroid hormone on vascular smooth muscle. Thyroid 5:505–512CrossRef Ojamaa K, Klemperer JD, Klein I (1996) Acute effects of thyroid hormone on vascular smooth muscle. Thyroid 5:505–512CrossRef
Zurück zum Zitat Pardridge WM, Buciak JL, Friden PM (1991) Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo. J Pharmacol Exp Ther 259:66–70PubMed Pardridge WM, Buciak JL, Friden PM (1991) Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo. J Pharmacol Exp Ther 259:66–70PubMed
Zurück zum Zitat Patel JP, Frey BN (2015) Disruption in the blood-brain barrier: the missing link between brain and body inflammation in bipolar disorder. Neural Plast 2015:1–12CrossRef Patel JP, Frey BN (2015) Disruption in the blood-brain barrier: the missing link between brain and body inflammation in bipolar disorder. Neural Plast 2015:1–12CrossRef
Zurück zum Zitat Perkonen F, Weintraub BD (1978) Thyrotropin binding to cultured lymphocytes and thyroid cells. Endocrinology 103:1668–1677CrossRef Perkonen F, Weintraub BD (1978) Thyrotropin binding to cultured lymphocytes and thyroid cells. Endocrinology 103:1668–1677CrossRef
Zurück zum Zitat Prummel MF, Brokken LJS, Meduri G, Misrahi M, Bakker O, Wiersinga WM (2000) Expression of the thyroid-stimulating hormone receptor in the folliculo-stellate cells of the human anterior pituitary. J Clin Endocrinol Metab 85:4347–4353CrossRefPubMed Prummel MF, Brokken LJS, Meduri G, Misrahi M, Bakker O, Wiersinga WM (2000) Expression of the thyroid-stimulating hormone receptor in the folliculo-stellate cells of the human anterior pituitary. J Clin Endocrinol Metab 85:4347–4353CrossRefPubMed
Zurück zum Zitat Raidoo DM, Ramsaroop R, Naidoo S, Bhoola KD (1996) Regional 2 distribution of tissue kallikrein in the human brain. Immunopharmacology 32:39–47CrossRefPubMed Raidoo DM, Ramsaroop R, Naidoo S, Bhoola KD (1996) Regional 2 distribution of tissue kallikrein in the human brain. Immunopharmacology 32:39–47CrossRefPubMed
Zurück zum Zitat Rojko JL, Price-Schiavi S (2008) Physiologic IgG biodistribution, transport, and clearance: implications for monoclonal antibody products. In: Cavagnaro JA (ed) Preclinical safety evaluation of biopharmaceuticals, vol Chapter 11. Wiley, Hoboken, pp 241–276CrossRef Rojko JL, Price-Schiavi S (2008) Physiologic IgG biodistribution, transport, and clearance: implications for monoclonal antibody products. In: Cavagnaro JA (ed) Preclinical safety evaluation of biopharmaceuticals, vol Chapter 11. Wiley, Hoboken, pp 241–276CrossRef
Zurück zum Zitat Sellitti DF (2000) Renal expression of two ‘thyroid-specific’ genes: thyrotropin receptor and thyroglobulin. Exp Nephrol 8:235–243CrossRefPubMed Sellitti DF (2000) Renal expression of two ‘thyroid-specific’ genes: thyrotropin receptor and thyroglobulin. Exp Nephrol 8:235–243CrossRefPubMed
Zurück zum Zitat Spitzweg C, Joba W, Heufelder AE (1999) Expression of thyroid-related genes in human thymus. Thyroid 9:133–141CrossRefPubMed Spitzweg C, Joba W, Heufelder AE (1999) Expression of thyroid-related genes in human thymus. Thyroid 9:133–141CrossRefPubMed
Zurück zum Zitat St-Amour I, Pare I, Alata W, Coulombe K (2013) Brain bioavailability of human intravenous immunoglobulin and its transport through the murine blood-brain barrier. J Cereb Blood Flow Metab 33:1983–1992CrossRefPubMedPubMedCentral St-Amour I, Pare I, Alata W, Coulombe K (2013) Brain bioavailability of human intravenous immunoglobulin and its transport through the murine blood-brain barrier. J Cereb Blood Flow Metab 33:1983–1992CrossRefPubMedPubMedCentral
Zurück zum Zitat Szkudlinski MW, Fremont V, Ronin C, Weintraub BD (2002) Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Physiol Rev 82:473–502CrossRefPubMed Szkudlinski MW, Fremont V, Ronin C, Weintraub BD (2002) Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Physiol Rev 82:473–502CrossRefPubMed
Zurück zum Zitat Terasaki T, Ohtsuki S (2005) Brain-to-blood transporters for endogenous substrates and xenobiotics at the blood-brain barrier: an overview of biology and methodology. NeuroRx 2:63–72CrossRefPubMedPubMedCentral Terasaki T, Ohtsuki S (2005) Brain-to-blood transporters for endogenous substrates and xenobiotics at the blood-brain barrier: an overview of biology and methodology. NeuroRx 2:63–72CrossRefPubMedPubMedCentral
Zurück zum Zitat Udayakumar N, Rameshkumar AC, Srinivasan AV (2005) Hoffmann syndrome: presentation in hypothyroidism. J Postgrad Med 51:332–333PubMed Udayakumar N, Rameshkumar AC, Srinivasan AV (2005) Hoffmann syndrome: presentation in hypothyroidism. J Postgrad Med 51:332–333PubMed
Zurück zum Zitat Valyasevi RW, Erickson DZ, Harteneck DA, Dutton CM, Heufelder AE (1999) Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. J Clin Endocrinol Metab 84:2557–2562PubMed Valyasevi RW, Erickson DZ, Harteneck DA, Dutton CM, Heufelder AE (1999) Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. J Clin Endocrinol Metab 84:2557–2562PubMed
Zurück zum Zitat Wright JK, Botha JH, Naidoo S (2008) Influence of the kallikrein-kinin system on prostate and breast tumour angiogenesis. Tumour Biol 29:130–136CrossRefPubMed Wright JK, Botha JH, Naidoo S (2008) Influence of the kallikrein-kinin system on prostate and breast tumour angiogenesis. Tumour Biol 29:130–136CrossRefPubMed
Zurück zum Zitat Yu F, Gothe S, Wikstrom L, Forest D, Vennstrom B, Larsson L (2000) Effects of thyroid hormone receptor gene disruption on myosin isoform expression in mouse skeletal muscles. Am J Phys Regul Integr Comp Phys 278:R1545–R1554 Yu F, Gothe S, Wikstrom L, Forest D, Vennstrom B, Larsson L (2000) Effects of thyroid hormone receptor gene disruption on myosin isoform expression in mouse skeletal muscles. Am J Phys Regul Integr Comp Phys 278:R1545–R1554
Metadaten
Titel
Expression of thyroid-stimulating hormone receptors and thyroglobulin in limbic regions in the adult human brain
verfasst von
Meleshni Naicker
Strinivasen Naidoo
Publikationsdatum
03.08.2017
Verlag
Springer US
Erschienen in
Metabolic Brain Disease / Ausgabe 2/2018
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-017-0076-3

Weitere Artikel der Ausgabe 2/2018

Metabolic Brain Disease 2/2018 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.