Skip to main content
Top
Published in: Journal of Endocrinological Investigation 1/2018

01-01-2018 | Short Review

The cell biology of the thyroid-disrupting mechanism of dichlorodiphenyltrichloroethane (DDT)

Authors: M. Rossi, A. R. Taddei, I. Fasciani, R. Maggio, F. Giorgi

Published in: Journal of Endocrinological Investigation | Issue 1/2018

Login to get access

Abstract

Objective

Dichlorodiphenyltrichloroethane (DDT) is an organochlorine known for its pesticide properties and for its negative effects on human health. It was banned in most countries for its toxicity to the endocrine system, but due to its persistence at clinically relevant concentrations in both soil and animal tissues, DDT is still linked to several health and social problems.

Methods

We have previously shown that DDT exposure is causally related to the extracellular release of vesicular organelles such as microvesicles and/or exosomes by using immunocytochemistry with gold-tagged antibodies and various fluorescent membrane markers.

Results

It is now well recognized that microvesicles and/or exosomes organelles are implicated in cell-to-cell communication, and that they are fundamental elements for transferring proteins, RNA, DNA, lipids and transcriptional factors among cells. In this short review, we discussed the role of extracellular vesicle formation in the thyroid-disrupting mechanism of DDT. In particular, we described how DDT, by dislodging the thyrotropin hormone (TSH) receptor from the raft containing compartments of the cells, prevents its activation and internalization.

Conclusion

Based on our earlier finding and on the large body of evidence here reviewed, we propose that DDT-induced formation of extracellular vesicles containing the TSH receptor could be directly involved in the development of autoimmune responses against the TSH receptor and that, therefore, their release could lead to the development of the Graves’ disease.
Literature
1.
go back to reference Coperchini F, Awwad O, Rotondi M, Santini F, Imbriani M, Chiovato L (2017) Thyroid disruption by perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). J Endocrinol Invest 40:105–121CrossRefPubMed Coperchini F, Awwad O, Rotondi M, Santini F, Imbriani M, Chiovato L (2017) Thyroid disruption by perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). J Endocrinol Invest 40:105–121CrossRefPubMed
3.
go back to reference Tilghman SL, Bratton MR, Segar HC, Martin EC, Rhodes LV, Li M, McLachlan JA, Wiese TE, Nephew KP, Burow ME (2012) Endocrine disruptor regulation of microRNA expression in breast carcinoma cells. PLoS ONE 7:e32754CrossRefPubMedPubMedCentral Tilghman SL, Bratton MR, Segar HC, Martin EC, Rhodes LV, Li M, McLachlan JA, Wiese TE, Nephew KP, Burow ME (2012) Endocrine disruptor regulation of microRNA expression in breast carcinoma cells. PLoS ONE 7:e32754CrossRefPubMedPubMedCentral
4.
go back to reference Ibhazehiebo K, Koibuchi N (2014) Impact of endocrine-disrupting chemicals on thyroid function and brain development. Expert Rev Endocrinol Metab 9:579–591CrossRef Ibhazehiebo K, Koibuchi N (2014) Impact of endocrine-disrupting chemicals on thyroid function and brain development. Expert Rev Endocrinol Metab 9:579–591CrossRef
5.
go back to reference Brar NK, Waggoner C, Reyes JA, Fairey R, Kelley KM (2010) Evidence for thyroid endocrine disruption in wild fish in San Francisco Bay, California, USA. Relationships to contaminant exposures. Aquat Toxicol 96:203–215CrossRefPubMed Brar NK, Waggoner C, Reyes JA, Fairey R, Kelley KM (2010) Evidence for thyroid endocrine disruption in wild fish in San Francisco Bay, California, USA. Relationships to contaminant exposures. Aquat Toxicol 96:203–215CrossRefPubMed
6.
go back to reference Freire C, Koifman RJ, Sarcinelli PN, Rosa AC, Clapauch R, Koifman S (2014) Association between serum levels of organochlorine pesticides and sex hormones in adults living in a heavily contaminated area in Brazil. Int J Hyg Environ Health 217:370–378CrossRefPubMed Freire C, Koifman RJ, Sarcinelli PN, Rosa AC, Clapauch R, Koifman S (2014) Association between serum levels of organochlorine pesticides and sex hormones in adults living in a heavily contaminated area in Brazil. Int J Hyg Environ Health 217:370–378CrossRefPubMed
7.
go back to reference Boas M, Feldt-Rasmussen U, Main KM (2012) Thyroid effects of endocrine disrupting chemicals. Mol Cell Endocrinol 355:240–248CrossRefPubMed Boas M, Feldt-Rasmussen U, Main KM (2012) Thyroid effects of endocrine disrupting chemicals. Mol Cell Endocrinol 355:240–248CrossRefPubMed
8.
go back to reference Müller CE, Schiedel AC, Baqi Y (2012) Allosteric modulators of rhodopsin-like G protein-coupled receptors: opportunities in drug development. Pharmacol Ther 135:292–315CrossRefPubMed Müller CE, Schiedel AC, Baqi Y (2012) Allosteric modulators of rhodopsin-like G protein-coupled receptors: opportunities in drug development. Pharmacol Ther 135:292–315CrossRefPubMed
10.
go back to reference Tschammer N (2016) Allosteric modulators of the class A G protein coupled receptors. Adv Exp Med Biol 917:185–207CrossRefPubMed Tschammer N (2016) Allosteric modulators of the class A G protein coupled receptors. Adv Exp Med Biol 917:185–207CrossRefPubMed
11.
go back to reference Santini F, Vitti P, Ceccarini G, Mammoli C, Rosellini V, Pelosini C, Marsili A, Tonacchera M, Agretti P, Santoni T, Chiovato L, Pinchera A (2003) In vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J Endocrinol Invest 26:950–955CrossRefPubMed Santini F, Vitti P, Ceccarini G, Mammoli C, Rosellini V, Pelosini C, Marsili A, Tonacchera M, Agretti P, Santoni T, Chiovato L, Pinchera A (2003) In vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J Endocrinol Invest 26:950–955CrossRefPubMed
12.
go back to reference Rossi M, Dimida A, Dell’anno MT, Trincavelli ML, Agretti P, Giorgi F, Corsini GU, Pinchera A, Vitti P, Tonacchera M, Maggio R (2007) The thyroid disruptor 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane appears to be an uncompetitive inverse agonist for the thyrotropin receptor. J Pharmacol Exp Ther 320:465–474CrossRefPubMed Rossi M, Dimida A, Dell’anno MT, Trincavelli ML, Agretti P, Giorgi F, Corsini GU, Pinchera A, Vitti P, Tonacchera M, Maggio R (2007) The thyroid disruptor 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane appears to be an uncompetitive inverse agonist for the thyrotropin receptor. J Pharmacol Exp Ther 320:465–474CrossRefPubMed
13.
go back to reference Rossi M, Dimida A, Ferrarini E, Silvano E, De Marco G, Agretti P, Aloisi G, Simoncini T, Di Bari L, Tonacchera M, Giorgi F, Maggio R (2009) Presence of a putative steroidal allosteric site on glycoprotein hormone receptors. Eur J Pharmacol 623:155–159CrossRefPubMed Rossi M, Dimida A, Ferrarini E, Silvano E, De Marco G, Agretti P, Aloisi G, Simoncini T, Di Bari L, Tonacchera M, Giorgi F, Maggio R (2009) Presence of a putative steroidal allosteric site on glycoprotein hormone receptors. Eur J Pharmacol 623:155–159CrossRefPubMed
14.
go back to reference De Gregorio F, Pellegrino M, Picchietti S, Belardinelli MC, Taddei AR, Fausto AM, Rossi M, Maggio R, Giorgi F (2011) The insecticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT) alters the membrane raft location of the TSH receptor stably expressed in Chinese hamster ovary cells. Toxicol Appl Pharmacol 253:121–129CrossRefPubMed De Gregorio F, Pellegrino M, Picchietti S, Belardinelli MC, Taddei AR, Fausto AM, Rossi M, Maggio R, Giorgi F (2011) The insecticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT) alters the membrane raft location of the TSH receptor stably expressed in Chinese hamster ovary cells. Toxicol Appl Pharmacol 253:121–129CrossRefPubMed
15.
go back to reference Calebiro D (2011) Thyroid-stimulating hormone receptor activity after internalization. Annales des Endocrinologie (Paris) 72:64–67CrossRef Calebiro D (2011) Thyroid-stimulating hormone receptor activity after internalization. Annales des Endocrinologie (Paris) 72:64–67CrossRef
16.
go back to reference Giorgi F, Auletta G (2016) Semiotic tools for multilevel cell communication. Biosemiotics 9:365–382CrossRef Giorgi F, Auletta G (2016) Semiotic tools for multilevel cell communication. Biosemiotics 9:365–382CrossRef
17.
go back to reference Sellitti DF, Akamizu T, Doi SQ, Kim GH, Kariyil JT, Kopchik JJ, Koshiyama H (2000) Renal expression of two ‘thyroid-specific’ genes: thyrotropin receptor and thyroglobulin. Exp Nephrol 8:235-243 Sellitti DF, Akamizu T, Doi SQ, Kim GH, Kariyil JT, Kopchik JJ, Koshiyama H (2000) Renal expression of two ‘thyroid-specific’ genes: thyrotropin receptor and thyroglobulin. Exp Nephrol 8:235-243
18.
go back to reference Williams GR (2011) Extrathyroidal expression of TSH receptor. Ann Endocrinol (Paris) 72:68–73CrossRef Williams GR (2011) Extrathyroidal expression of TSH receptor. Ann Endocrinol (Paris) 72:68–73CrossRef
19.
go back to reference Pierce KL, Premont RT, Lefkowitz RJ (2002) Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3:639–650CrossRefPubMed Pierce KL, Premont RT, Lefkowitz RJ (2002) Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3:639–650CrossRefPubMed
20.
go back to reference Allgeier A, Offermanns S, Van Sande J, Spicher K, Schultz G, Dumont JE (1994) The human thyrotropin receptor activates G-proteins Gs and Gq/11. J Biol Chem 269:13733–13735PubMed Allgeier A, Offermanns S, Van Sande J, Spicher K, Schultz G, Dumont JE (1994) The human thyrotropin receptor activates G-proteins Gs and Gq/11. J Biol Chem 269:13733–13735PubMed
21.
go back to reference Couët J, de Bernard S, Loosfelt H, Saunier B, Milgrom E, Misrahi M (1996) Cell surface protein disulfide-isomerase is involved in the shedding of human thyrotropin receptor ectodomain. Biochemistry 35:14800–14805CrossRefPubMed Couët J, de Bernard S, Loosfelt H, Saunier B, Milgrom E, Misrahi M (1996) Cell surface protein disulfide-isomerase is involved in the shedding of human thyrotropin receptor ectodomain. Biochemistry 35:14800–14805CrossRefPubMed
22.
go back to reference Couët J, Sar S, Jolivet A, Hai MT, Milgrom E, Misrahi M (1996) Shedding of human thyrotropin receptor ectodomain. Involvement of a matrix metalloprotease. J Biol Chem 271:4545–4552CrossRefPubMed Couët J, Sar S, Jolivet A, Hai MT, Milgrom E, Misrahi M (1996) Shedding of human thyrotropin receptor ectodomain. Involvement of a matrix metalloprotease. J Biol Chem 271:4545–4552CrossRefPubMed
23.
go back to reference Misrahi M, Couet J, Milgrom E (1997) Mechanisms of shedding of a soluble form of the TSH receptor. Ann Endocrinol (Paris) 58:365–369 Misrahi M, Couet J, Milgrom E (1997) Mechanisms of shedding of a soluble form of the TSH receptor. Ann Endocrinol (Paris) 58:365–369
24.
go back to reference Latif R, Ando T, Davies TF (2004) Monomerization as a prerequisite for intramolecular cleavage and shedding of the thyrotropin receptor. Endocrinology 145:5580–5588CrossRefPubMed Latif R, Ando T, Davies TF (2004) Monomerization as a prerequisite for intramolecular cleavage and shedding of the thyrotropin receptor. Endocrinology 145:5580–5588CrossRefPubMed
25.
go back to reference Maggio R, Innamorati G, Parenti M (2007) G protein-coupled receptor oligomerization provides the framework for signal discrimination. J Neurochem 103:1741–1752CrossRefPubMed Maggio R, Innamorati G, Parenti M (2007) G protein-coupled receptor oligomerization provides the framework for signal discrimination. J Neurochem 103:1741–1752CrossRefPubMed
26.
go back to reference Scarselli M, Annibale P, McCormick PJ, Kolachalam S, Aringhieri S, Radenovic A, Corsini GU, Maggio R (2016) Revealing G-protein-coupled receptor oligomerization at the single-molecule level through a nanoscopic lens: methods, dynamics and biological function. FEBS J 283:1197–1217CrossRefPubMed Scarselli M, Annibale P, McCormick PJ, Kolachalam S, Aringhieri S, Radenovic A, Corsini GU, Maggio R (2016) Revealing G-protein-coupled receptor oligomerization at the single-molecule level through a nanoscopic lens: methods, dynamics and biological function. FEBS J 283:1197–1217CrossRefPubMed
27.
go back to reference Giorgi F, Bruni LE, Maggio R (2010) Receptor oligomerization as a process modulating cellular semiotics. Biosemiotics 3:157–176CrossRef Giorgi F, Bruni LE, Maggio R (2010) Receptor oligomerization as a process modulating cellular semiotics. Biosemiotics 3:157–176CrossRef
28.
go back to reference Baratti-Elbaz C, Ghinea N, Lahuna O, Loosfelt H, Pichon C, Milgrom E (1999) Internalization and recycling pathways of the thyrotropin receptor. Mol Endocrinol 13:1751–1765CrossRefPubMed Baratti-Elbaz C, Ghinea N, Lahuna O, Loosfelt H, Pichon C, Milgrom E (1999) Internalization and recycling pathways of the thyrotropin receptor. Mol Endocrinol 13:1751–1765CrossRefPubMed
29.
go back to reference Singh SP, McDonald D, Hope TJ, Prabhakar BS (2004) Upon thyrotropin binding the thyrotropin receptor is internalized and localized to endosome. Endocrinology 145:1003–1010CrossRefPubMed Singh SP, McDonald D, Hope TJ, Prabhakar BS (2004) Upon thyrotropin binding the thyrotropin receptor is internalized and localized to endosome. Endocrinology 145:1003–1010CrossRefPubMed
30.
go back to reference Hoffmann C, Gaietta G, Bünemann M, Adams SR, Oberdorff-Maass S, Behr B, Vilardaga J-P, Tsien RY, Ellisman MH, Lohse MJ (2005) A FlAsH-based FRET approach to determine G protein—coupled receptor activation in living cells. Nat Methods 2:171–176CrossRefPubMed Hoffmann C, Gaietta G, Bünemann M, Adams SR, Oberdorff-Maass S, Behr B, Vilardaga J-P, Tsien RY, Ellisman MH, Lohse MJ (2005) A FlAsH-based FRET approach to determine G protein—coupled receptor activation in living cells. Nat Methods 2:171–176CrossRefPubMed
31.
go back to reference Picchietti S, Belardinelli M, Taddei AR, Fausto AM, Pellegrino M, Maggio R, Rossi M, Giorgi F (2009) Thyroid disruptor 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT) prevents internalization of TSH receptor. Cell Tissue Research 336:31–40CrossRefPubMed Picchietti S, Belardinelli M, Taddei AR, Fausto AM, Pellegrino M, Maggio R, Rossi M, Giorgi F (2009) Thyroid disruptor 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT) prevents internalization of TSH receptor. Cell Tissue Research 336:31–40CrossRefPubMed
32.
go back to reference Cornelia W, Ferguson SSG (2015) Minireview: role of intracellular scaffolding proteins in the regulation of endocrine G protein-coupled receptor signaling. Mol Endocrinol 29:814–830CrossRef Cornelia W, Ferguson SSG (2015) Minireview: role of intracellular scaffolding proteins in the regulation of endocrine G protein-coupled receptor signaling. Mol Endocrinol 29:814–830CrossRef
33.
go back to reference De Azua IR, Nakajima K-I, Rossi M, Cui Y, Jou W, Gavrilova O, Wess J (2012) Spinophilin as a novel regulator of M3 muscarinic receptor-mediated insulin release in vitro and in vivo. FASEB J 26:4275–4286CrossRef De Azua IR, Nakajima K-I, Rossi M, Cui Y, Jou W, Gavrilova O, Wess J (2012) Spinophilin as a novel regulator of M3 muscarinic receptor-mediated insulin release in vitro and in vivo. FASEB J 26:4275–4286CrossRef
34.
go back to reference Latif R, Ando T, Davies TF (2007) Lipid rafts are triage centers for multimeric and monomeric thyrotropin receptor regulation. Endocrinology 148:3164–3175CrossRefPubMed Latif R, Ando T, Davies TF (2007) Lipid rafts are triage centers for multimeric and monomeric thyrotropin receptor regulation. Endocrinology 148:3164–3175CrossRefPubMed
35.
go back to reference Del Conde I, Shrimpton CN, Thiagarajan P, López JA (2005) Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106:1604–1611CrossRefPubMed Del Conde I, Shrimpton CN, Thiagarajan P, López JA (2005) Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106:1604–1611CrossRefPubMed
36.
go back to reference Baciu AE, Uyy E, Uică VI, Boteanu RM, Popescu AI, Giulea C, Manda D, Badiu C, Antohe F (2017) Proteomic analysis of plasma molecular markers as predictors of differentiated thyroid cancer. Rom Rep Phys 69:601 Baciu AE, Uyy E, Uică VI, Boteanu RM, Popescu AI, Giulea C, Manda D, Badiu C, Antohe F (2017) Proteomic analysis of plasma molecular markers as predictors of differentiated thyroid cancer. Rom Rep Phys 69:601
37.
go back to reference Muralidharan-Chari V, Clancy JW, Sedgwick A, D’Souza-Schorey C (2010) Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 123:1603–1611CrossRefPubMedPubMedCentral Muralidharan-Chari V, Clancy JW, Sedgwick A, D’Souza-Schorey C (2010) Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 123:1603–1611CrossRefPubMedPubMedCentral
38.
go back to reference Rodríguez-Muñoz A, Martínez-Hernández R, Ramos-Leví AM, Serrano-Somavilla A, González-Amaro R, Sánchez-Madrid F, de la Fuente H, Marazuela M (2015) Circulating microvesicles regulate treg and th17 differentiation in human autoimmune thyroid disorders. J Clin Endocrinol Metabol 100:E1531–E1539CrossRef Rodríguez-Muñoz A, Martínez-Hernández R, Ramos-Leví AM, Serrano-Somavilla A, González-Amaro R, Sánchez-Madrid F, de la Fuente H, Marazuela M (2015) Circulating microvesicles regulate treg and th17 differentiation in human autoimmune thyroid disorders. J Clin Endocrinol Metabol 100:E1531–E1539CrossRef
39.
go back to reference Mobarrez F, Abraham-Nordling M, Aguilera-Gatica K, Friberg I, Antovic A, Pisetsky DS, Jörneskog G, Wallen H (2016) The expression of microvesicles in the blood of patients with Graves’ disease and its relationship to treatment. Clin Endocrinol (Oxf) 84:729–735CrossRef Mobarrez F, Abraham-Nordling M, Aguilera-Gatica K, Friberg I, Antovic A, Pisetsky DS, Jörneskog G, Wallen H (2016) The expression of microvesicles in the blood of patients with Graves’ disease and its relationship to treatment. Clin Endocrinol (Oxf) 84:729–735CrossRef
40.
go back to reference Vlasov P, Doi SQ, Sellitti DF (2016) FRTL-5 Rat Thyroid cells release thyroglobulin sequestered in exosomes: a possible novel mechanism for thyroglobulin processing in the thyroid. J Tyroid Res 2016:9276402 Vlasov P, Doi SQ, Sellitti DF (2016) FRTL-5 Rat Thyroid cells release thyroglobulin sequestered in exosomes: a possible novel mechanism for thyroglobulin processing in the thyroid. J Tyroid Res 2016:9276402
41.
go back to reference Marinò M, McCluskey RT (2000) Role of thyroglobulin endocytic pathways in the control of thyroid hormone release. Am J Physiol Cell Physiol 279:C1295–C1306CrossRefPubMed Marinò M, McCluskey RT (2000) Role of thyroglobulin endocytic pathways in the control of thyroid hormone release. Am J Physiol Cell Physiol 279:C1295–C1306CrossRefPubMed
42.
go back to reference Botta R, Lisi S, Pinchera A, Taddei AR, Fausto AM, Giorgi F, Marinò M (2011) Binding, uptake, and degradation of internalized thyroglobulin in cultured thyroid and non-thyroid cells. J Endocrinol Invest 34:515–520PubMed Botta R, Lisi S, Pinchera A, Taddei AR, Fausto AM, Giorgi F, Marinò M (2011) Binding, uptake, and degradation of internalized thyroglobulin in cultured thyroid and non-thyroid cells. J Endocrinol Invest 34:515–520PubMed
43.
go back to reference Lisi S, Botta R, Rotondo Dottore G, Leo M, Latrofa F, Vitti P, Marinò M (2016) Intracellular retention of thyroglobulin in the absence of the low-density lipoprotein receptor-associated protein (RAP) is likely due to premature binding to megalin in the biosynthetic pathway. J Endocrinol Invest 39:1039–1044CrossRefPubMed Lisi S, Botta R, Rotondo Dottore G, Leo M, Latrofa F, Vitti P, Marinò M (2016) Intracellular retention of thyroglobulin in the absence of the low-density lipoprotein receptor-associated protein (RAP) is likely due to premature binding to megalin in the biosynthetic pathway. J Endocrinol Invest 39:1039–1044CrossRefPubMed
44.
go back to reference Botta R, Lisi S, Rotondo Dottore G, Vitti P, Marinò M (2017) Binding of thyroglobulin (Tg) to the low-density lipoprotein receptor-associated protein (RAP) during the biosynthetic pathway prevents premature Tg interactions with sortilin. J Endocrinol Invest. doi: 10.1007/s40618-017-0668-0. (Epub ahead of print) Botta R, Lisi S, Rotondo Dottore G, Vitti P, Marinò M (2017) Binding of thyroglobulin (Tg) to the low-density lipoprotein receptor-associated protein (RAP) during the biosynthetic pathway prevents premature Tg interactions with sortilin. J Endocrinol Invest. doi: 10.​1007/​s40618-017-0668-0. (Epub ahead of print)
45.
go back to reference Hakulinen J, Sankkila L, Sugiyama N, Kaisa Lehti K, Keski-Oja J (2008) Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes. J Cell Biochem 105:1211–1218CrossRefPubMed Hakulinen J, Sankkila L, Sugiyama N, Kaisa Lehti K, Keski-Oja J (2008) Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes. J Cell Biochem 105:1211–1218CrossRefPubMed
47.
go back to reference Masci VL, Taddei AR, Gambellini G, Giorgi F, Fausto AM (2016) Microvesicles shed from fibroblasts act as metalloproteinase carriers in a 3D collagen matrix. J Circ Biomark 5:1–11CrossRef Masci VL, Taddei AR, Gambellini G, Giorgi F, Fausto AM (2016) Microvesicles shed from fibroblasts act as metalloproteinase carriers in a 3D collagen matrix. J Circ Biomark 5:1–11CrossRef
48.
go back to reference Dahlman T, Grimelius L, Wallin G, Rubin K, Westermark K (1998) Integrins in thyroid tissue: upregulation of a2b1 in anaplastic thyroid carcinoma. Eur J Endocrinol 138:104–112CrossRefPubMed Dahlman T, Grimelius L, Wallin G, Rubin K, Westermark K (1998) Integrins in thyroid tissue: upregulation of a2b1 in anaplastic thyroid carcinoma. Eur J Endocrinol 138:104–112CrossRefPubMed
49.
go back to reference Cayrol F, Díaz Flaqué MC, Fernando T, Yang SN, Sterle HA, Bolontrade M, Amorós M, Isse B, Farías RN, Ahn H, Tian YF, Tabbò F, Singh A, Inghirami G, Cerchietti L, Cremaschi GA (2015) Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells. Blood 125:841–851CrossRefPubMedPubMedCentral Cayrol F, Díaz Flaqué MC, Fernando T, Yang SN, Sterle HA, Bolontrade M, Amorós M, Isse B, Farías RN, Ahn H, Tian YF, Tabbò F, Singh A, Inghirami G, Cerchietti L, Cremaschi GA (2015) Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells. Blood 125:841–851CrossRefPubMedPubMedCentral
50.
go back to reference Davies TF, Latif R (2015) Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies. Expert Opin Ther Targets 19:835–847CrossRefPubMedPubMedCentral Davies TF, Latif R (2015) Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies. Expert Opin Ther Targets 19:835–847CrossRefPubMedPubMedCentral
51.
go back to reference Tan L, Wu H, Liu Y, Zhao M, Li D, Lu Q (2016) Recent advances of exosomes in immune modulation and autoimmune diseases. J Autoimmun 49:357–365CrossRef Tan L, Wu H, Liu Y, Zhao M, Li D, Lu Q (2016) Recent advances of exosomes in immune modulation and autoimmune diseases. J Autoimmun 49:357–365CrossRef
52.
go back to reference Gallo A, Tandon M, Alevizos I, Illei GG (2012) The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 7(3):e30679CrossRefPubMedPubMedCentral Gallo A, Tandon M, Alevizos I, Illei GG (2012) The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 7(3):e30679CrossRefPubMedPubMedCentral
Metadata
Title
The cell biology of the thyroid-disrupting mechanism of dichlorodiphenyltrichloroethane (DDT)
Authors
M. Rossi
A. R. Taddei
I. Fasciani
R. Maggio
F. Giorgi
Publication date
01-01-2018
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation / Issue 1/2018
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-017-0716-9

Other articles of this Issue 1/2018

Journal of Endocrinological Investigation 1/2018 Go to the issue

Acknowledgements to Referees

Thanks to Reviewers 2017

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.