pax2.1is required for the development of thyroid follicles in zebrafish

Development ◽  
2002 ◽  
Vol 129 (15) ◽  
pp. 3751-3760 ◽  
Author(s):  
Thomas Wendl ◽  
Klaus Lun ◽  
Marina Mione ◽  
Jack Favor ◽  
Michael Brand ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Marker Gene ◽  
Follicular Cells ◽  
Hormone Production ◽  
Zebrafish Model ◽  
Hormone Synthesis ◽  
Larval Stages ◽  
Thyroid Follicular Cells ◽  
Thyroid Development

The thyroid gland is an organ primarily composed of endoderm-derived follicular cells. Although disturbed embryonic development of the thyroid gland leads to congenital hypothyroidism in humans and mammals, the underlying principles of thyroid organogenesis are largely unknown. In this study, we introduce zebrafish as a model to investigate the molecular and genetic mechanisms that control thyroid development. Marker gene expression suggests that the molecular pathways of early thyroid development are essentially conserved between fish and mammals. However during larval stages, we find both conserved and divergent features of development compared with mammals. A major difference is that in fish, we find evidence for hormone production not only in thyroid follicular cells, but also in an anterior non-follicular group of cells.We show that pax2.1 and pax8, members of the zebrafish pax2/5/8 paralogue group, are expressed in the thyroid primordium. Whereas in mice, only Pax8 has a function during thyroid development, analysis of the zebrafish pax2.1 mutant no isthmus (noi–/–) demonstrates that pax2.1 has a role comparable with mouse Pax8 in differentiation of the thyroid follicular cells. Early steps of thyroid development are normal in noi–/–, but later expression of molecular markers is lost and the formation of follicles fails. Interestingly, the anterior non-follicular site of thyroid hormone production is not affected in noi–/–. Thus, in zebrafish, some remaining thyroid hormone synthesis takes place independent of the pathway leading to thyroid follicle formation. We suggest that the noi–/– mutant serves as a new zebrafish model for hypothyroidism.

scholarly journals Primary congenital hypothyroidism: defects in iodine pathways

2003 ◽  
pp. 247-256 ◽  
Author(s):  
JJ de Vijlder
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Primary Hypothyroidism ◽  
Special Importance ◽  
Hormone Production ◽  
Central Hypothyroidism ◽  
Hormone Synthesis ◽  
Diagnosis And Classification ◽  
The Central Nervous System

The thyroid gland is the only source of thyroid hormone production. Thyroid hormone is essential for growth and development, and is of special importance for the development of the central nervous system. It was for that reason that neonatal screening on congenital hypothyroidism was introduced and is now performed in many countries. Defects in thyroid hormone production are caused by several disorders in hormone synthesis and in the development of the thyroid gland (primary hypothyroidism) or of the pituitary gland and hypothalamus (central hypothyroidism).This paper describes defects in the synthesis of thyroid hormone caused by disorders in the synthesis or iodination of thyroglobulin, leakage of iodinated proteins by a stimulated thyroid gland and the presence of abnormal iodoproteins, mainly iodinated albumin, in the thyroid gland and blood circulation. Circulating thyroglobulin and abnormal iodoproteins, as well as the breakdown products of these iodoproteins excreted in urine, are used for etiological diagnosis and classification. Moreover, our finding of an enzyme that catalyses the dehalogenation of iodotyrosines, which is important for iodine recycling and required for economical use of iodine, is also referred to.

scholarly journals Thyroglobulin gene mutations and other genetic defects associated with congenital hypothyroidism

2004 ◽  
Vol 48 (1) ◽  
pp. 70-82 ◽  
Author(s):  
Jussara Vono-Toniolo ◽  
Peter Kopp
Keyword(s):  
Thyroid Hormone ◽  
Congenital Hypothyroidism ◽  
Early Recognition ◽  
Wide Spectrum ◽  
Hormone Deficiency ◽  
Follicular Cells ◽  
Thyroid Dysgenesis ◽  
Hormone Synthesis ◽  
Screening Programs ◽  
Thyroid Follicular Cells

Congenital hypothyroidism affects about 1:3000-1:4000 infants. Screening programs now permit early recognition and treatment, thus avoiding the disastrous consequences of thyroid hormone deficiency on brain development. In about 85%, congenital hypothyroidism is associated with developmental defects referred to as thyroid dysgenesis. They include thyroid (hemi)agenesis, ectopic tissue and thyroid hypoplasia. Thyroid dysgenesis is usually sporadic; in only 2% it occurs in a familial fashion. It can be caused by mutations in transcription factors that are essential for the development and function of thyroid follicular cells. Thyroid hypoplasia can also result from resistance to TSH at the level of the thyrocytes. Defects in the steps required for thyroid hormone synthesis within thyroid follicular cells are referred to as dyshormonogenesis and account for about 10-15% of congenital hypothyroidism. In contrast to thyroid dysgenesis, affected patients typically present with goitrous enlargement of the thyroid. The defects leading to dyshormonogenesis typically display a recessive mode of inheritance. Careful clinical, biochemical and molecular analyses of patients with syndromic and non-syndromic forms of thyroid dysgenesis and dyshormonogenesis have significantly enhanced our understanding of the wide spectrum of pathogenetic mechanisms underlying congenital hypothyroidism and provide unique insights into the (patho)physiology of thyroid development and hormone synthesis.

scholarly journals Generation of Adult Stem Cell Derived Organoid Cultures From Thyroid Follicular Cells

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A850-A851
Author(s):  
Jelte van der Vaart ◽  
Lynn Bosmans ◽  
Hanneke Margo van Santen ◽  
Menno R Vriens ◽  
Hans Clevers
Keyword(s):  
Stem Cell ◽  
Thyroid Hormone ◽  
Culture System ◽  
Adult Stem Cell ◽  
Human Thyroid ◽  
Wild Type ◽  
Follicular Cells ◽  
Hormone Production ◽  
Organoid Culture ◽  
Thyroid Follicular Cells

Abstract The thyroid is essential for maintaining systemic homeostasis by regulating thyroid hormone concentrations in the bloodstream. Due to the limited number of representative model systems, there is limited understanding of fundamental thyroid biology as well as thyroid carcinogenesis. To fill the caveats in the understanding of thyroid cell biology, we aimed to develop an adult stem cell-derived three-dimensional (3D) organoid culture system using murine and human thyroid follicular cells (TFCs). We have succeeded to grow such an organoid culture system that harbours the complete machinery of hormone production visualised by the presence of colloid in the lumen and essential transporters and enzymes in a polarised cell layer. Both the established murine as human thyroid organoids express canonical thyroid markers PAX8 and NKX2.1/TTF1. Moreover, the thyroid hormone precursor thyroglobulin is expressed in both cultures to similar levels as in tissue. Extensive characterisation furthermore identifies known and new biological insights in TFC subclassification, subcellular organisation and hormone production using state-of-the art techniques like single cell RNA sequencing, transmission electron microscopy and genome editing. These 3D in vitro cultures allow for a variety of thyroid-related studies including the progression of wild type cells towards cancer. Additionally, due to the success of generating patient-specific tumour organoids of primary differentiated thyroid carcinoma and metastasis, insights in drug resistance and metastases can be identified. In short, this newly developed organoid culture of murine and human wild type TFCs as well as tumour tissue opens up an extensive area of research that will help understand the drivers for growth and development of thyroid (cancer) cells and enable studies upon drug responsiveness.

scholarly journals Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism

2021 ◽  
Vol 118 (51) ◽  
pp. e2117017118
Author(s):  
Jelte van der Vaart ◽  
Lynn Bosmans ◽  
Stijn F. Sijbesma ◽  
Kèvin Knoops ◽  
Willine J. van de Wetering ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Secretion ◽  
Thyroid Tissue ◽  
Three Dimensional ◽  
Disease Patient ◽  
Human Thyroid ◽  
Follicular Cells ◽  
Hormone Production ◽  
Transmission Electron ◽  
Thyroid Follicular Cells

The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of three-dimensional (3D) organoids from adult thyroid tissue representing murine and human thyroid follicular cells (TFCs). The TFC organoids (TFCOs) harbor the complete machinery of hormone production as visualized by the presence of colloid in the lumen and by the presence of essential transporters and enzymes in the polarized epithelial cells that surround a central lumen. Both the established murine as human thyroid organoids express canonical thyroid markers PAX8 and NKX2.1, while the thyroid hormone precursor thyroglobulin is expressed at comparable levels to tissue. Single-cell RNA sequencing and transmission electron microscopy confirm that TFCOs phenocopy primary thyroid tissue. Thyroid hormones are readily detectable in conditioned medium of human TFCOs. We show clinically relevant responses (increased proliferation and hormone secretion) of human TFCOs toward a panel of Graves’ disease patient sera, demonstrating that organoids can model human autoimmune disease.

scholarly journals Red snapper fish intake improves thyroid gland activity in the hypothyroidism rat

Food Research ◽  
2021 ◽  
Vol 5 (S2) ◽  
pp. 18-24
Author(s):  
E. Herawati ◽  
R.S. Titisari ◽  
S.A.N. Husna ◽  
O.P. Astirin ◽  
T. Widiyani ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Positive Control ◽  
Negative Control ◽  
Red Snapper ◽  
Female Rats ◽  
Hormone Production ◽  
Remarkable Change ◽  
Hormone Synthesis ◽  
Thyroid Gland Activity

Congenital hypothyroidism is inadequate production of thyroid hormone in infants from birth. Treatment of hypothyroidism often involves an iodine-rich diet since iodine is a vital precursor for thyroid hormone synthesis. Red snapper fish is a saltwater fish that contain a high amount of iodine and other beneficial macro/micronutrients, yet no report was found on the effect of this fish consumption on hypothyroidism. The objective of this study was to determine the effectiveness of red snapper (Lutjanus sp.) fish on thyroid gland activity, manifested by low FT4 level and high TSH level, two diagnostic indicators of hypothyroidism. This study used a post-test and controlled group design. Pregnant female rats were given propylthiouracil orally for four weeks to induce hypothyroidism in their offspring. All hypothyroid offspring were divided into five treatment groups, i.e., negative control, positive control (thyroxin therapy), red snapper enriched diet at 25% and 50% dosage, also a combination of levothyroxine and red snapper. The thyroid gland activity was detected by measuring blood serum FT4 and TSH and histological examination of the thyroid gland using HE staining. The level of FT4 and TSH in each treatment group were analyzed with the one-way ANOVA test. The results showed that the group that received a 50% red snapper diet has a normal level of FT4 and TSH, whereas the FT4 level increased two-fold; the TSH level decreased significantly. The organization of the thyroid gland showed a remarkable change of the lumen diameter, indicating a higher amount of hormone production by the gland.

scholarly journals AMIODARON SEBAGAI OBAT ANTI ARITMIA DAN PENGARUHNYA TERHADAP FUNGSI TIROID

2013 ◽  
Vol 3 (2) ◽  
Author(s):  
Starry H. Rampengan
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Thyroid Function ◽  
Hormone Replacement ◽  
Type I ◽  
Peripheral Tissues ◽  
Hormone Synthesis ◽  
Thyroid Hormone Metabolism ◽  
Serum T4 ◽  
Life Threatening

Abstract: Amiodarone is a highly effective anti-arrhythmic agent used in certain arrhythmias from supraventricular tachycardia to life-threatening ventricular tachycardia. Its use is associated with numerous side-effects that could deteriorate a patient’s condition. Consequently, a clinician should consider the risks and benefits of amiodarone before initiating the treatment.The thyroid gland is one of the organs affected by amiodarone. Amiodarone and its metabolite desethyl amiodaron induce alterations in thyroid hormone metabolism in the thyroid gland, peripheral tissues, and probably also in the pituitary gland. These actions result in elevations of serum T4 and rT3 concentrations, transient increases in TSH concentrations, and decreases in T3 concentrations. Both hypothyroidism and hyperthyroidism are prone to occur in patients receiving amiodarone. Amiodarone-induced hypothyroidism (AIH) results from the inability of the thyroid to escape from the Wolff-Chaikoff effect and is readily managed by either discontinuation of amiodarone or thyroid hormone replacement. Amiodarone-induced thyrotoxicosis (AIT) may arise from either iodine-induced excessive thyroid hormone synthesis (type I, usually with underlying thyroid abnormality), or destructive thyroiditis with release of preformed hormones (type II, commonly with apparently normal thyroid glands). Therefore, monitoring of thyroid function should be performed in all amiodarone-treated patients to facilitate early diagnosis and treatment of amiodarone-induced thyroid dysfunction. Key words: Amiodarone, thyroid function, side effect, management, monitoring.     Abstrak: Amiodaron adalah obat antiaritmia yang cukup efektif dalam menangani beberapa keadaaan aritmia mulai dari supraventrikuler takikardia sampai takikardia ventrikuler yang mengancam kehidupan. Namun penggunaan obat ini ternyata menimbulkan efek samping pada organ lain yang dapat menimbulkan perburukan keadaan pasien. Sehingga, dalam penggunaan amiodaron, klinisi juga harus menimbang keuntungan dan kerugian yang ditimbulkan oleh obat ini. Salah satu organ yang dipengaruhi oleh amiodaron adalah kelenjar tiroid. Amiodaron dan metabolitnya desetil amiodaron memengaruhi hormon tiroid pada kelenjar tiroid, jaringan perifer, dan mungkin pada pituitari. Aksi amiodaron ini menyebabkan peningkatan T4, rT3 dan TSH, namun menurunkan kadar T3. Hipotiroidisme dan tirotoksikosis dapat terjadi pada pasien yang diberi amiodaron. Amiodarone-induced hypothyroidism (AIH) terjadi karena ketidakmampuan tiroid melepaskan diri dari efek Wolff Chaikof, dan dapat ditangani dengan pemberian  hormon substitusi T4 atau penghentian amiodaron. Amiodarone-induced thyrotoxicosis (AIT) terjadi karena sintesis hormon tiroid yang berlebihan yang diinduksi oleh iodium (tipe I, biasanya sudah mempunyai kelainan tiroid sebelumnya) atau karena tiroiditis destruktif yang disertai pelepasan hormon tiroid yang telah terbentuk (tipe II, biasanya dengan kelenjar yang normal). Pemantauan fungsi tiroid seharusnya dilakukan pada semua pasien yang diberi amiodaron untuk memfasilitasi diagnosis dan terapi yang dini terjadinya  disfungsi tiroid yang diinduksi amiodaron. Kata Kunci: Amiodaron, fungsi tiroid, efek samping, penanganan, pemantauan.

Iodide Metabolism and Effects

2020 ◽  
pp. 25-33
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Thyroid Hormones ◽  
Dietary Supplement ◽  
Thyroid Function ◽  
Thyroid Stimulating Hormone ◽  
Hormone Synthesis ◽  
Serum Tsh ◽  
Tsh Stimulation ◽  
Sensitive Marker

Iodine (I2) is essential in the synthesis of thyroid hormones T4 and T3 and functioning of the thyroid gland. Both T3 and T4 are metabolically active, but T3 is four times more potent than T4. Our body contains 20-30 mg of I2, which is mainly stored in the thyroid gland. Iodine is naturally present in some foods, added to others, and available as a dietary supplement. Serum thyroid stimulating hormone (TSH) level is a sensitive marker of thyroid function. Serum TSH is increased in hypothyroidism as in Hashimoto's thyroiditis. In addition to regulation of thyroid function, TSH promotes thyroid growth. If thyroid hormone synthesis is chronically impaired, TSH stimulation eventually may lead to the development of a goiter. This chapter explores the iodide metabolism and effects of Hashimoto's disease.

Stimulation of Na(+)-K(+)-ATPase by thyrotropin in cultured thyroid follicular cells

1995 ◽  
Vol 268 (5) ◽  
pp. C1252-C1258 ◽  
Author(s):  
T. A. Pressley ◽  
S. C. Higham ◽  
L. A. Joson ◽  
D. W. Mercer
Keyword(s):  
Thyroid Stimulating Hormone ◽  
Follicular Cells ◽  
Hormone Synthesis ◽  
Metabolic Turnover ◽  
Striking Increase ◽  
Thyroid Follicular Cells ◽  
A Cell ◽  
Messenger System ◽  
Rat Thyroid ◽  
Stimulation Of

Thyroid-stimulating hormone (TSH; thyrotropin) produces a pleiotropic response in the thyroid gland, accelerating nearly every aspect of metabolic turnover within the follicular epithelia. We examined the effects of TSH on expression of Na(+)-K(+)-ATPase in FRTL-5 cells, a cell line derived from rat thyroid. TSH (10 mU/ml) produced a nearly twofold increase in abundance of the mRNA encoding the catalytic alpha 1-subunit within 6 h of treatment. With the four mRNAs encoding the beta 1-subunit, TSH produced a striking increase in abundance, but this regulation was discoordinate, and some species increased more than others. Similar increases in mRNA abundance were elicited by activators of the adenosine 3',5'-cyclic monophosphate second messenger system. In contrast to the alpha 1- and beta 1-mRNAs, the abundance of the mRNA encoding the beta 2-subunit was unchanged with TSH after 6 h, indicating that the effects of thyrotropin were not universal or indiscriminate. Thyrotropin also caused a 76% increase in Na(+)-K(+)-ATPase activity and a 46% increase in pump-mediated transport after 48 h. These studies suggest that the changes in metabolic turnover initiated by TSH during hormone synthesis include upregulation of the N(+)-K+ pump.

scholarly journals Thyroid hormone transporters

2005 ◽  
Vol 33 (1) ◽  
pp. 228-232 ◽  
Author(s):  
E.C.H. Friesema ◽  
J. Jansen ◽  
T.J Visser
Keyword(s):  
Biological Activity ◽  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Cell Membrane ◽  
Human Chromosome ◽  
Elevated Serum ◽  
Psychomotor Retardation ◽  
Follicular Cells ◽  
Serum T3 ◽  
T3 Receptors

Thyroid hormone is important for development of various tissues, in particular brain, and for regulation of metabolic processes throughout life. The follicular cells of the thyroid gland produce predominantly T4 (thyroxine), but the biological activity of thyroid hormone is largely exerted by T3 (3,3′,5-tri-iodothyronine). The deiodinases involved in T4-to-T3 conversion or T4 and T3 degradation, as well as the T3 receptors, are located intracellularly. Therefore the action and metabolism of thyroid hormone require transport of iodothyronines across the cell membrane via specific transporters. Recently, a number of transporters capable of cellular uptake of iodothyronines have been identified. The most specific transporters identified so far are OATP1C1 and MCT8, which appear to be involved in T4 transport across the blood–brain barrier, and in T3 transport into brain neurons, respectively. The MCT8 gene is located on human chromosome Xq13, and mutations in MCT8 are associated with X-linked severe psychomotor retardation and elevated serum T3 levels.

Thyrotrophin-releasing hormone (TRH) and hormone secretion from the follicular and C-cells of perfused dog thyroid lobes

1985 ◽  
Vol 109 (4) ◽  
pp. 499-504 ◽  
Author(s):  
E. Iversen ◽  
P. Laurberg
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
C Cells ◽  
Follicular Cells ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Direct Inhibitory Effect ◽  
Thyroid Secretion

Abstract. Recently we found small amounts of TRH immunoreactivity in the thyroid gland of dogs and pigs. In the present study we investigated if exogenous TRH influences the release of T4, T3 and cAMP from the follicular cells, and calcitonin and somatostatin from the C-cells of perfused dog thyroid lobes. 10−5 mol/l TRH inhibited the TSH induced iodothyronine and cAMP release from the thyroid while 10−8 mol/l TRH had no effect. The relative proportions of T4 and T3 in thyroid secretion were not altered by TRH infusion. TRH did not influence the basal or the Ca++ induced release of somatostatin and calcitonin. Hence TRH has a direct inhibitory effect on the hormone secretion from thyroidal follicular cells. This opens the possibility that TRH in the thyroid participate in the regulation of thyroid hormone secretion. Even though the concentration of TRH found to be effective is high our results may indicate that TRH in the thyroid participates in the regulation of thyroid hormone secretion as an antagonist to TSH.

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