Talk:Endocrine - Thyroid Development

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On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes: References - recent and historic that relates to the topic Additional topic information - currently prepared in draft format Links - to related webpages Topic page - an edit history as used on other Wiki sites Lecture/Practical - student feedback Student Projects - online project discussions. Links: Pubmed Most Recent | Reference Tutorial | Journal Searches Glossary Links Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link Cite this page: Hill, M.A. (2024, April 27) Embryology Endocrine - Thyroid Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Endocrine_-_Thyroid_Development

2011

Do Thyroid Disrupting Chemicals Influence Foetal Development during Pregnancy?

J Thyroid Res. 2011;2011:342189. Epub 2011 Sep 11.

Hartoft-Nielsen ML, Boas M, Bliddal S, Rasmussen AK, Main K, Feldt-Rasmussen U. Source Department of Medical Endocrinology PE-2131, Rigshospitalet, University Hospital of Copenhagen, 2100 Copenhagen, Denmark.

Abstract

Maternal euthyroidism during pregnancy is crucial for normal development and, in particular, neurodevelopment of the foetus. Up to 3.5 percent of pregnant women suffer from hypothyroidism. Industrial use of various chemicals-endocrine disrupting chemicals (EDCs)-has been shown to cause almost constant exposure of humans with possible harmful influence on health and hormone regulation. EDCs may affect thyroid hormone homeostasis by different mechanisms, and though the effect of each chemical seems scarce, the added effects may cause inappropriate consequences on, for example, foetal neurodevelopment. This paper focuses on thyroid hormone influence on foetal development in relation to the chemicals suspected of thyroid disrupting properties with possible interactions with maternal thyroid homeostasis. Knowledge of the effects is expected to impact the general debate on the use of these chemicals. However, more studies are needed to elucidate the issue, since human studies are scarce.

PMID 21918727 PMC3170895

Identification of Novel Pax8 Targets in FRTL-5 Thyroid Cells by Gene Silencing and Expression Microarray Analysis

PLoS One. 2011;6(9):e25162. Epub 2011 Sep 23.

Di Palma T, Conti A, de Cristofaro T, Scala S, Nitsch L, Zannini M. Source Institute of Experimental Endocrinology and Oncology 'G. Salvatore' (IEOS), National Research Council, Naples, Italy.

Abstract

BACKGROUND: The differentiation program of thyroid follicular cells (TFCs), by far the most abundant cell population of the thyroid gland, relies on the interplay between sequence-specific transcription factors and transcriptional coregulators with the basal transcriptional machinery of the cell. However, the molecular mechanisms leading to the fully differentiated thyrocyte are still the object of intense study. The transcription factor Pax8, a member of the Paired-box gene family, has been demonstrated to be a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well-characterized with respect to its role in regulating genes involved in thyroid differentiation, genomics approaches aiming at the identification of additional Pax8 targets are lacking and the biological pathways controlled by this transcription factor are largely unknown.

METHODOLOGY/PRINCIPAL FINDINGS: To identify unique downstream targets of Pax8, we investigated the genome-wide effect of Pax8 silencing comparing the transcriptome of silenced versus normal differentiated FRTL-5 thyroid cells. In total, 2815 genes were found modulated 72 h after Pax8 RNAi, induced or repressed. Genes previously reported to be regulated by Pax8 in FRTL-5 cells were confirmed. In addition, novel targets genes involved in functional processes such as DNA replication, anion transport, kinase activity, apoptosis and cellular processes were newly identified. Transcriptome analysis highlighted that Pax8 is a key molecule for thyroid morphogenesis and differentiation.

CONCLUSIONS/SIGNIFICANCE: This is the first large-scale study aimed at the identification of new genes regulated by Pax8, a master regulator of thyroid development and differentiation. The biological pathways and target genes controlled by Pax8 will have considerable importance to understand thyroid disease progression as well as to set up novel therapeutic strategies.

PMID 21966443

Hes1 Is Required for Appropriate Morphogenesis and Differentiation during Mouse Thyroid Gland Development

PLoS One. 2011 Feb 25;6(2):e16752.

Carre A, Rachdi L, Tron E, Richard B, Castanet M, Schlumberger M, Bidart JM, Szinnai G, Polak M.

INSERM U845, Université Paris-Descartes, Paris, France.

Abstract

Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1(-/-) mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1(-/-) mouse embryos showed a significantly smaller total thyroid surface area (-40 to -60%) compared to wild type mice at all study time points (E9.5-E16.5). In both Hes1(-/-) and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1(-/-) mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1(-/-) thyroids revealed a significantly decreased labelling area for T4 (-78%) and calcitonin (-65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (-69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells.

PMID 21364918 http://www.ncbi.nlm.nih.gov/pubmed/21364918

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016752

2010

Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity

Cereb Cortex. 2010 Jun;20(6):1462-75. Epub 2009 Oct 7.

Berbel P, Navarro D, Ausó E, Varea E, Rodríguez AE, Ballesta JJ, Salinas M, Flores E, Faura CC, de Escobar GM.

Instituto de Neurociencias, Universidad Miguel Hernández and Consejo Superior de Investigaciones Científicas, Sant Joan d'Alacant, Alicante, Spain. pere.berbel@umh.es Abstract Hypothyroxinemia affects 35-50% of neonates born prematurely (12% of births) and increases their risk of suffering neurodevelopmental alterations. We have developed an animal model to study the role of maternal thyroid hormones (THs) at the end of gestation on offspring's cerebral maturation. Pregnant rats were surgically thyroidectomized at embryonic day (E) 16 and infused with calcitonin and parathormone (late maternal hypothyroidism [LMH] rats). After birth, pups were nursed by normal rats. Pups born to LMH dams, thyroxine treated from E17 to postnatal day (P) 0, were also studied. In developing LMH pups, the cortical lamination was abnormal. At P40, heterotopic neurons were found in the subcortical white matter and in the hippocampal stratum oriens and alveus. The Zn-positive area of the stratum oriens of hippocampal CA3 was decreased by 41.5% showing altered mossy fibers' organization. LMH pups showed delayed learning in parallel to decreased phosphorylated cAMP response element-binding protein (pCREB) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression in the hippocampus. Thyroxine treatment of LMH dams reverted abnormalities. In conclusion, maternal THs are still essential for normal offspring's neurodevelopment even after onset of fetal thyroid function. Our data suggest that thyroxine treatment of premature neonates should be attempted to compensate for the interruption of the maternal supply.

PMID 19812240

Surgical anatomy of the thyroid and parathyroid glands

Otolaryngol Clin North Am. 2010 Apr;43(2):221-7, vii.

Fancy T, Gallagher D 3rd, Hornig JD.

Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. Abstract This article describes the anatomy and embryology of the thyroid and parathyroid glands and the recurrent laryngeal nerve, discussing how the anatomy affects function and dysfunction of the glands.

PMID 20510710

2009

Thyroid dysfunction and kidney disease

Eur J Endocrinol. 2009 Apr;160(4):503-15. Epub 2008 Dec 18.

Iglesias P, Díez JJ.

Department of Endocrinology, Hospital Ramón y Cajal, Carretera de Colmenar, Madrid, Spain. piglo65@gmail.com Abstract Thyroid hormones (TH) are essential for an adequate growth and development of the kidney. Conversely, the kidney is not only an organ for metabolism and elimination of TH, but also a target organ of some of the iodothyronines' actions. Thyroid dysfunction causes remarkable changes in glomerular and tubular functions and electrolyte and water homeostasis. Hypothyroidism is accompanied by a decrease in glomerular filtration, hyponatremia, and an alteration of the ability for water excretion. Excessive levels of TH generate an increase in glomerular filtration rate and renal plasma flow. Renal disease, in turn, leads to significant changes in thyroid function. The association of different types of glomerulopathies with both hyper- and hypofunction of the thyroid has been reported. Less frequently, tubulointerstitial disease has been associated with functional thyroid disorders. Nephrotic syndrome is accompanied by changes in the concentrations of TH due primarily to loss of protein in the urine. Acute kidney injury and chronic kidney disease are accompanied by notable effects on the hypothalamus-pituitary-thyroid axis. The secretion of pituitary thyrotropin (TSH) is impaired in uremia. Contrary to other non-thyroidal chronic disease, in uraemic patients it is not unusual to observe the sick euthyroid syndrome with low serum triodothyronine (T(3)) without elevation of reverse T(3) (rT(3)). Some authors have reported associations between thyroid cancer and kidney tumors and each of these organs can develop metastases into the other. Finally, data from recent research suggest that TH, especially T(3), can be considered as a marker for survival in patients with kidney disease.

PMID 19095779

http://www.ncbi.nlm.nih.gov/pubmed/19095779

http://eje-online.org/cgi/content/full/160/4/503

Early thyroid development requires a Tbx1-Fgf8 pathway.

Dev Biol. 2009 Apr 1;328(1):109-17. Epub 2009 Jan 20.

Lania G, Zhang Z, Huynh T, Caprio C, Moon AM, Vitelli F, Baldini A.

Telethon Institute of Genetics and Medicine, and University Federico II, Naples, Italy. Abstract The thyroid develops within the pharyngeal apparatus from endodermally-derived cells. The many derivatives of the pharyngeal apparatus develop at similar times and sometimes from common cell types, explaining why many syndromic disorders express multiple birth defects affecting different structures that share a common pharyngeal origin. Thus, different derivatives may share common genetic networks during their development. Tbx1, the major gene associated with DiGeorge syndrome, is a key player in the global development of the pharyngeal apparatus, being required for virtually all its derivatives, including the thyroid. Here we show that Tbx1 regulates the size of the early thyroid primordium through its expression in the adjacent mesoderm. Because Tbx1 regulates the expression of Fgf8 in the mesoderm, we postulated that Fgf8 mediates critical Tbx1-dependent interactions between mesodermal cells and endodermal thyrocyte progenitors. Indeed, conditional ablation of Fgf8 in Tbx1-expressing cells caused an early thyroid phenotype similar to that of Tbx1 mutant mice. In addition, expression of an Fgf8 cDNA in the Tbx1 domain rescued the early size defect of the thyroid primordium in Tbx1 mutants. Thus, we have established that a Tbx1->Fgf8 pathway in the pharyngeal mesoderm is a key size regulator of mammalian thyroid.

PMID 19389367

Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review.

Zimmermann MB. Am J Clin Nutr. 2009 Feb;89(2):668S-72S. Epub 2008 Dec 16. Review. PMID 19088150

Classification and etiology of congenital hypothyroidism

Classification	Etiology
Primary	Thyroid dysgenesis (developmental anomaly) Thyroid dyshormonogenesis (impaired hormone production) Resistance to TSH binding or signaling
Central	Isolated TSH deficiency Thyrotropin-releasing hormone deficiency Thyrotropin-releasing hormone resistance Deficiency in pituitary development transcription factors
Peripheral	Resistance to thyroid hormone Abnormalities of thyroid hormone transport
Syndromic	Pendred syndrome Bamforth-Lazarus syndrome Ectodermal dysplasia Hypothyroidism Kocher - Deber - Semilange syndrome Benign chorea - hypothyroidism Choreoathetosis Obesity - colitis
Transient	Maternal intake of antithyroid drugs Transplacental passage of maternal TSH receptor blocking antibodies Maternal and neonatal iodine deficiency or excess Heterozygous mutations of THOX2 or DUOXA2 Congenital hepatic hemangioma/hemangioendothelioma
	Based on Table 3 from review on congenital hypothyroidism.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526509/

Congenital Hypothyroidism

The Italian National Register of infants with congenital hypothyroidism: twenty years of surveillance and study of congenital hypothyroidism Olivieri A, The Study Group for Congenital Hypothyroidism Italian Journal of Pediatrics 2009, 35:2 (20 February 2009)

http://www.ijponline.net/content/35/1/2

thyroglossal duct

• thyroglossal duct cyst is the most common congenital anomaly of the thyroid gland

Some Recent Findings

Food Standards Australia New Zealand (FSANZ) - 22nd Australian Total Diet Study A total diet study of five trace elements: iodine, selenium, chromium, molybdenum, and nickel (More? [../Defect/page11.htm Abnormal Development - Iodine Deficiency] | [../Notes/endocrine8.htm Endocrine Development - Thyroid]

"Whilst the majority of Australians had dietary intakes approaching or above the estimated average requirement (EAR) or AI for selenium, molybdenum and chromium, a substantial proportion of the population had iodine intakes below the EAR. FSANZ has subsequently commissioned further analyses of iodine levels in Australian foods and will be introducing mandatory fortification of iodine in bread, from September 2009."

Goodman JH, Gilbert ME. Modest Thyroid Hormone Insufficiency during Development Induces a Cellular Malformation in the Corpus Callosum: A Model of Cortical Dysplasia. Endocrinology. 2007 Jun;148(6):2593-7. (Rodent study)

American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS; Public Health Committee, Lawson Wilkins Pediatric Endocrine Society, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK.Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006 Jun;117(6):2290-303. Review. PMID: 16740880

Park SM, Chatterjee VK. Genetics of congenital hypothyroidism. J Med Genet. 2005 May;42(5):379-89.

"Congenital hypothyroidism is the most common neonatal metabolic disorder and results in severe neurodevelopmental impairment and infertility if untreated. Congenital hypothyroidism is usually sporadic but up to 2% of thyroid dysgenesis is familial, and congenital hypothyroidism caused by organification defects is often recessively inherited.... This review focuses on the genetic aspects of primary congenital hypothyroidism."

John Hopkins Medical Institute Wolfberg, Adam J. and David A. Nagey Abstract # 274: Thyroid Disease During Pregnancy and Subsequent Congenital Anomalies.

The researchers studied 101 women (64 with hypothyroidism and 50 with the overactive version, hyperthyroidism) who gave birth at The Johns Hopkins Hospital between December 1994 and June 1999.

• 108 pregnancies with 114 fetuses
• 21 babies (18%) had birth defects (including cardiac, renal and central nervous systems and other disorders such as sunken chest, extra fingers, cleft lip and palate, and ear deformities)
• 2 fetuses died before being delivered

(More? Thyroid disease 'raises birth risk' Women with thyroid disease are more likely have babies with birth defects even if tests show no problem with the gland during pregnancy, say Johns Hopkins University researchers (BBC report Jan 20, 2002).

Reading

• Human Embryology (2nd ed.) Larson
• The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch10: p230-233, Ch12: p280-282, Ch13: p319-347
• Before We Are Born (5th ed.) Moore and Persaud
• Essentials of Human Embryology Larson
• Human Embryology Fitzgerald and Fitzgerald Ch24: p166-167

Development Overview

24 days - thyroid median endodermal thickening in the floor of pharynx outpouch – thyroid diverticulum.

Week 11 - colloid appearance in thyroid follicles, iodine and thyroid hormone (TH) synthesis. growth factors (insulin-like, epidermal) stimulates follicular growth.

Fetal - thyroid hormone initial secreted biologically inactivated by modification, late fetal secretion develops brown fat. Iodine deficiency- during this period, leads to neurological defects (cretinism).

Birth - TSH levels increase, thyroxine (T3) and T4 levels increase to 24 h, then 5-7 days postnatal decline to normal levels.

Hypothalamic-thyroid (HPT) axis development

Serial Images

Stage 13/14 Embryo: [../wwwpig/pigb/b1l.htm B1- section showing hypopharyngeal eminence] | [../wwwpig/pigb/b2l.htm B2- section showing developing thyroid cells in hypopharyngeal eminence] | [../wwwpig/pigb/b3l.htm B3- section showing developing thyroid]

Stage 22 Human Embryo: [../wwwhuman/lowpower/HumC/C4L.htm C4- portion of Thyroid lateral to trachea] (note anterior of section missing) | [../wwwhuman/lowpower/HumC/C5L.htm C5- portion of Thyroid anterior to trachea] | [../wwwhuman/lowpower/HumC/C6L.htm C6- connecting stalk between Thyroid and Parathyroid]

Stage 22 Human Embryo High Power: [../wwwhuman/hipower/HumC/C3L.htm HPC3- cross-section of developing Thyroid] | [../wwwhuman/hipower/HumC/C2L.htm HPC2-Location of this Section]

Stage 13/14 Images

File:St13b1.gif[../wwwpig/pigb/b1l.htm B1] Superior portion of hypopharyngeal eminence lying in arch of Pharynx.

[../wwwpig/pigb/b2l.htm B2] The primordial Thyroid cords (dark spots) in the Pharynx floor. Note Rathke's pouch in the midline of Pharynx roof.

[../wwwpig/pigb/b2l.htm B2]Dark spots within the hypopharyngeal eminence are the "cords" of thyroid precursor cells descending from the pharynx floor to form the thyroid gland in the neck. Thyroid has an important endocrine role in later development.

[../wwwpig/pigb/B3L.htm B3]: Rudimentary thyroid ventral to aortic sac (also seen in B2, ventral to the hypopharyngeal eminence).

High Power Images

File:HumHPC2.gifC2 Human 27mm Embryo File:HumHPC3L.gifC3 Human 27mm Embryo

Transthyretin

Transthyretin - (TTR, prealbumin) the serum protein which acts as a major carrier of thyroid hormones in the blood.

The protein can also bind plasma retinol-binding protein and may therefore regulate retinoid availability.

Links: OMIM - Transthyretin

Abnormalities

Congenital hypothyroidism - approximately 1 in 3000 births, associated with neurological abnormalities.

Lingual thyroid gland - failure of thyroid descent.

Thyroglossal cyst - persistance of thyroglossal duct.

Thyroglossal fistula - partial degeneration of the thyroglossal duct.

Abnormal development of the thyroid - incomplete or excessive descent.

Pyramidal lobe - from isthmus (50% of people) attached to hyoid bone distal end of thryoglossal duct.

Childhood hypothyroidism delays ossification and bone mineralization.

(See also NIH Genes & Disease Chapter 41 - Endocrine)

Iodine Deficiency

Iodine deficiency disorder (IDD) is the single most common cause of preventable mental retardation and brain damage in the world (More? [../Defect/page11.htm Abnormal Development - Iodine Deficiency]). It is required for synthesis of thyroid hormone, which in turn regulates aspects of neural development.

Worldwide:

• 1.6 billion people are at risk
• IDD affects 50 million children
• 100,000 cretins are born every year

It causes goiters and decreases the production of hormones vital to growth and development. Children with IDD can grow up stunted, apathetic, mentally retarded and incapable of normal movement, speech or hearing. IDD in pregnant women cause miscarriage, stillbirth and mentally retarded children.

A teaspoon of iodine is all a person requires in a lifetime, but because iodine cannot be stored for long periods by the body, tiny amounts are needed regularly. In areas of endemic iodine deficiency, where soil and therefore crops and grazing animals do not provide sufficient dietary iodine to the populace, food fortification and supplementation have proven highly successful and sustainable interventions.

Iodized salt programs and iodized oil supplements are the most common tools in the fight against IDD.

(Data: ICCIDD)

Prolonged intake of large amounts (excess) of iodide can increase the incidence of goiter and/or hypothyroidism in humans. African Congo appears to be the only country that appears to have a dietary excess.

Links: International Council for the Control of Iodine Deficiency Disorders | Australian Centre for Control of Iodine Deficiency Disorders | Asia-Pacific Iodine Nutrition Map (ICCID)

(More? [../Defect/page11.htm Abnormal Development - Iodine Deficiency])

Maternal Thyroid

Maternal thyroid related changes during pregnancy:

• stimulation of maternal thyroid gland by elevated levels of human chorionic gonadotropin (hCG)
  • occurs mainly near end of first trimester associated with a transient lowering in serum TSH
• increase in serum thyroxine-binding globulin levels
• small decrease in free hormone concentrations (in iodine-sufficient conditions) significantly amplified in iodine restriction or overt iodine deficiency
• trend toward a slight increase in basal thyrotropin (TSH) values between first trimester and term
• modifications of the peripheral metabolism of maternal thyroid hormones

(Text modified from : Glinoer D. What happens to the normal thyroid during pregnancy? Thyroid. 1999 Jul;9(7):631-5.)

Maternal Abnormalities

File:10.1371 journal.pmed.0020370.g002-M.jpg	(A) Normal (B) Graves disease: diffuse increased uptake in both thyroid lobes. (C) Toxic multinodular goiter (TMNG): “hot” and “cold” areas of uneven uptake. (D) Toxic adenoma: increased uptake in a single nodule with suppression of the surrounding thyroid. (E) Thyroiditis: decreased or absent uptake. Image: Perros P. Thyrotoxicosis and pregnancy. PLoS Med. 2005 Dec;2(12):e370.
Thyroid Uptake Scans (Technetium 99)

Maternal Graves Disease - "The dose of anti-thyroid drug usually needs to be decreased during pregnancy, and often Graves disease remits completely and the medication can be withdrawn. This is probably due to the overall immunosuppressive effect of pregnancy." (Perros P. Thyrotoxicosis and pregnancy. PLoS Med. 2005 Dec;2(12):e370.)

Graves' disease in mothers can cause thyrotoxic fetus - may have increased fetal motility and develop a range of abnormalities including: goitre, tachycardia, heart failure associated hydrops, growth retardation, craniosynostosis and accelerated bone maturation.

Maternal Hashimoto's Thyroiditis (common autoimmune thyroid disease) usually no consequences on fetal thyroid, even if antibodies (anti-TPO and anti-Tg) found in the newborn due to transplacental passage.

maternal hypothyroxinemia

Links: NIH Genes & Disease - Chapter 41 - Endocrine | EPA (USA) - Radiation Technetium

Environmental Thyroid Disruptors

There are several environmental compounds (chemicals) that are suspected of being thyroid disruptors including:

• halogenated phenolic compounds (3,3',5,5'-tetrabromobisphenol A, 3,3',5,5'-tetrachlorobisphenol A, 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl)
• phenol compounds (pentachlorophenol, 2,4,6-triiodophenol)

They have been demonstrated to induce partial agonistic and/or complex competitive/uncompetitive antagonistic responces in cell culture.

Bisphenol A - monomer used to manufacture polycarbonate plastic, possibly disrupts thyroid hormone function and affects neocortical development (accelerating neuronal differentiation/migration). (More? EHP - Bisphenol A Need for a New Risk Assessment)

Genes

Thyroid Transcriptor Factors (TTF) - TTF-1, TTF-2, PAX-8

Fetal hypothyroidism from low levels of these transcription factors- Pit-1, Prop-1, LHX-3

Thyrotropin-releasing hormone (TRH)

Thyroid-stimulating hormone (TSH)

References

Links: [#Journals Journals] | [#OnlineTextbooks Online Textbooks] | [#SearchTextbooks Search Textbooks] | [#PubMed PubMed] | [#1999Refs 1999 Refs] | [#SearchPubMed Search PubMed] | [#Glossary Glossary]

Journals

Thyroid Thyroid The official journal of the [%20http://www.thyroid.org/ American Thyroid Association].

Online Textbooks

Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001. table of Contents

• The Thyroid Gland
• Surgical anatomy and embryology of the thyroid gland
• Hypothyroidism in infancy and childhood

NIH Genes & Disease Chapter 41 - Endocrine

Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.

• Is the endostyle the precursor of the thyroid gland?
• Environmental thyroid hormone disruptors
• table 13.1. Some derivatives of the neural crest

Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002.

• table 15-1. Some Hormone-induced Cell Responses Mediated by Cyclic AMP

Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct.

• Thyroid Gland search Results

Search NLM Online Textbooks "thyroid development" : Endocrinology | Molecular Biology of the Cell | The Cell- A molecular Approach

PubMed

Reviews

• Postiglione MP, Parlato R, Rodriguez-Mallon A, Rosica A, Mithbaokar P, Maresca M, Marians RC, Davies TF, Zannini MS, De Felice M, Di Lauro R. Role of the thyroid-stimulating hormone receptor signaling in development and differentiation of the thyroid gland. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15462-7.
• Park SM, Chatterjee VK. Genetics of congenital hypothyroidism. J Med Genet. 2005 May;42(5):379-89.
• De Felice M, Postiglione MP, Di Lauro R. Minireview: thyrotropin receptor signaling in development and differentiation of the thyroid gland: insights from mouse models and human diseases. Endocrinology. 2004 Sep;145(9):4062-7. Epub 2004 Jul 1. Review
• Gruters A, Biebermann H, Krude H. Neonatal thyroid disorders. Horm Res. 2003;59 Suppl 1:24-9. Review.

Articles

• Villa-Cuesta E, Modolell J. Mutual repression between msh and Iro-C is an essential component of the boundary between body wall and wing in Drosophila. Development. 2005 Aug 10
• Iskaros J, Pickard M, Evans I, Sinha A, Hardiman P, Ekins R. Thyroid hormone receptor gene expression in first trimester human fetal brain. J Clin Endocrinol Metab. 2000 Jul;85(7):2620-3.

Search PubMed

Search Jun2006 "thyroid development" 9,551 reference articles of which 1,703 were reviews.

Search PubMed: term= thyroid+development

Thyroid Development (1999)

• Follicular cells of the thyroid gland require Pax8 gene function. Mansouri A, Chowdhury K, Gruss P Nat Genet 1998 May;19(1):87-90
  • "The thyroid gland develops from two distinct embryonic lineages: follicular cells (which produce thyroxine) and parafollicular C-cells (which produce calcitonin) are of endodermal and neural crest origin, respectively. Little is known about the molecular mechanisms governing the generation of these different cell types. Mice lacking the transcription factor Ttf1 lack both cell types and thus are unable to develop a thyroid gland. By analysis of Pax8-/- mice, we demonstrate that Pax8 is required for the formation of the follicular cells in the thyroid. We present evidence that Pax8 is necessary for providing cues for the differentiation of competent endoderm primordia into thyroxin-producing follicular cells."
• TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation. Zannini M, Avantaggiato V, Biffali E, Arnone MI, Sato K, Pischetola M, Taylor BA, Phillips SJ, Simeone A, Di Lauro R EMBO J 1997 Jun 2;16(11):3185-97
  • "Expression of thyroglobulin (Tg) and thyroperoxidase (TPO) genes in thyroid follicular cells occurs in the mouse at embryonic day (E)14.5. Two transcription factors, TTF-1 and Pax-8, have been implicated in transcriptional activation of Tg and TPO, even though the onset of their expression is at E9.5, suggesting that additional events are necessary for transcriptional activation of Tg and TPO genes. We report in this paper the cloning of TTF-2, a DNA binding protein that recognizes sites on both Tg and TPO promoters. TTF-2 is a new forkhead domain-containing protein whose expression is restricted to the endodermal lining of the foregut and to the ectoderm that will give rise to the anterior pituitary. TTF-2 shows transient expression in the developing thyroid and anterior pituitary. In the thyroid, TTF-2 expression is down-regulated just before the onset of Tg and TPO gene expression, suggesting that this transcription factor plays the role in development of a negative controller of thyroid-specific gene expression."
• Regulation of thyroid hormone metabolism during fetal development. Darras VM, Hume R, Visser TJ Mol Cell Endocrinol 1999 May 25;151(1-2):37-47 PubMed
  • "Compared with adults, plasma T3 concentrations in the human fetus are decreased, whereas levels of rT3 and the different iodothyronine sulfates, T4S, T3S, rT3S and 3,3'-T2S, are increased. The low T3 and high rT3 concentrations reflect the preponderance of inner ring versus outer ring deiodinase activity due to high type III iodothyronine deiodinase (D3) expression in fetal tissues, such as liver and brain, the placenta, and perhaps also the uterus, in combination with still incomplete expression of hepatic type I iodothyronine deiodinase (D1) expression. In contrast to humans, D3 is hardly expressed in the fetal rat liver. However, high D3 expression is observed in the embryonic chicken liver which decreases dramatically towards the end of incubation, resulting in a marked increase in plasma T3. Thyroid hormone is essential for the development of the brain, in which local conversion of the prohormone T4 to the active hormone T3 by the type II iodothyronine deiodinase (D2) plays a very important role. In contrast to the rat, however, little is known about the ontogeny of D2 in different human brain areas. The cause of the high concentrations of sulfated iodothyronines in fetal plasma is unknown. In adults, the liver is an important site for the clearance of these conjugates, where they are rapidly degraded by D1. Although fetal human liver expresses significant D1 activity, clearance of iodothyronine sulfates may be defective due to the lack of transporters mediating their hepatic uptake. However, production of iodothyronine sulfates may also be increased in the human fetus, although the responsible sulfotransferases and their location remain to be identified. Sulfation may be a reversible pathway of thyroid hormone inactivation, depending on the recovery of free hormone by sulfatases. However, little is known at present about the characteristics and regulation of these enzymes in fetal human tissues. Further studies are required to increase our understanding of the tissue-specific and stage-dependent regulation of thyroid hormone bioactivity during human development."
• Hormone synthesis and storage in the thyroid of human preterm and term newborns: effect of thyroxine treatment. van den Hove MF, Beckers C, Devlieger H, de Zegher F, De Nayer P Biochimie 1999 May;81(5):563-70
  • "Iodine and thyroglobulin concentrations, as well as iodine, T3, T4 and sialic acid contents of thyroglobulin, were measured in thyroid glands collected postmortem from 42 human premature or term newborns and infants. Three groups were considered: very preterm newborns (24-32 postmenstrual weeks, < 5 days postnatal life), preterm and term newborns (34-41 postmenstrual weeks, < 5 days postnatal life) and infants (born at term, postnatal age 1-8 months). Five very preterm and seven preterm newborns received a daily dose of 10 microg/kg L-T4 for at least 3 days. Thyroid weight and sialic acid content of thyroglobulin progressed with maturation. Intrathyroidal concentrations of iodine and thyroglobulin did not increase significantly before the 42nd week of postmenstrual age. The level of thyroglobulin iodination increased during the postnatal life, except in the very preterm neonates. T4 and T3 content of thyroglobulin was directly proportional to its degree of iodination and positively related to its sialic acid content. L-T4 treatment of preterm newborns increased thyroglobulin iodination and T4-T3 content, without increasing thyroglobulin concentration in the thyroid. It was concluded that the storage of thyroglobulin and iodine in the thyroid develops around term birth. This, associated with the resulting rapid theoretical turnover of the intrathyroidal pool of T4 in Tg, could be an important factor of increased risk of neonatal hypothyroxinemia in the premature infants. The L-T4 treatment of preterm newborns does not accelerate the maturational process of the thyroid gland."

External Links

• International Council for the Control of Iodine Deficiency Disorders
• World Health Organization- Micronutrient deficiencies Eliminating iodine deficiency disorders
• British Thyroid Association The official site of the British Thyroid Assocation, a non-profit making Learned Society of professional clinical specialist doctors and scientists in the United Kingdom who manage patients with thyroid disease and/or are researching into the thyroid and its diseases in humans.
• WHO Nutrition Guidelines
• American Thyroid Association American Thyroid Association - Patient Information
• [www.clark.net/pub/tfa/index.html Thyroid Foundation of America]
• Endocrine Society (USA)
• European Thyroid Association
• Latin-American Thyroid Association
• [www.aota.or.kr Asia and Oceana Thyroid Association]
• Society for Endocrinology (UK)
• British Association of Endocrine Surgeons
• [www.aace.com American Association of Clinical Endocrinologists]
• Thyroid Disease Manager USA -- this site includes textbook on the Thyroid.
• [www.synthroid.com Knoll Pharmaceuticals]- makers of SYNTHROID
• Gray's Anatomy- 4. The Ductless Glands
  • The thyroid gland and its relations
  • Floor of pharynx of human embryo about twenty-six days old. (From model by Peters)
  • 4b. The Parathyroid Glands

Internal LinksEndocrine

[endocrine.htm Introduction][endocrine2.htm Abnormalities][endocrine3.htm Stage 13/14][endocrine4.htm Stage 22][endocrine5.htm Selected Stage 22]Thyroid[endocrine7.htm Pituitary][endocrine9.htm Adrenal][endocrine10.htm Pancreas][endocrine12.htm Pineal][endocrine13.htm Thymus][endocrine15.htm Gonad][endocrine14.htm Placenta][endocrine15.htm Gonads][endocrine16.htm Hypothalmus][endocrine17.htm Parathyroid][endocrine18.htm Adipose Tissue][endocrine19.htm Other Tissues][endocrine11.htm Molecular][endocrinelink.htm Web Links]