Cryo-EM structure of native human thyroglobulin

The thyroglobulin (TG) protein is essential to thyroid hormone synthesis, plays a vital role in the regulation of metabolism, development and growth and serves as intraglandular iodine storage. Its architecture is conserved among vertebrates. Synthesis of triiodothyronine (T3) and thyroxine (T4) hormones depends on the conformation, iodination and post-translational modification of TG. Although structural information is available on recombinant and deglycosylated endogenous human thyroglobulin (hTG) from patients with goiters, the structure of native, fully glycosylated hTG remained unknown. Here, we present the cryo-electron microscopy structure of native and fully glycosylated hTG from healthy thyroid glands to 3.2 Å resolution. The structure provides detailed information on hormonogenic and glycosylation sites. We employ liquid chromatography–mass spectrometry (LC-MS) to validate these findings as well as other post-translational modifications and proteolytic cleavage sites. Our results offer insights into thyroid hormonogenesis of native hTG and provide a fundamental understanding of clinically relevant mutations.

Clinical aspects of morphological investigation of fetal thyroid glands

The investigation of 121 thyroid glands offetuses and neonates of mothers who live in Saint-Petersburg was carried out. The paper analyzes intra and postnatal fatal outcomes taking account оf gestational andpostnatal age. The role of thyroid glands adaptive function emaciation in thanatogenesis in case of asphyxia was demonstrated. On the basis of the study practical recommendations are suggested.

SOME TOPOGRAPHICAL AND HISTOLOGICAL STUDIES OF THYROID AND PARATHYROD GLANDS OF MOORHEN (Gallinula c. chloropus)

The thyroid gland of Moorhen has two separated lobes. These lobes were located in the throracic inlet and receive blood supply from the cranial, middle and caudal thyroid arteries. The histological organization of the thyroid gland in Moorhen is surrounded by a distinct connective tissue capsule and the parenchymal cells were arranged into colloid filled follicles enmeshed in the highly vascular interstitial connective tissue. The bilaterally paired, round to oval, parathyroid glands in Moorhen were located intrathoracically near or close to the caudal pole of the thyroid glands. They receive blood by short branches from caudal thyroid artery and small branch from the common carotid artery. The parathyroid glands in Moorhen have a thin connective tissue capsule. Its parenchymal cells were arranged into an irregular, anastomosing cords of chief cells. No oxyphil cells were found in the parathyroid glands of Moorhen.

Diffuse Alopecia and Thyroid Atrophy in Sheep

Thyroid dysfunction substantially affects the quality of life due to its association with various disorders in different organs. A low intake of selenium and zinc can predispose to thyroid alterations, resulting in hypothyroidism. A deficiency of selenium and zinc causes direct and indirect skin lesions, both by the action of free radicals on the skin and by thyroid dysfunction. The aim of this study was to describe natural cases of diffuse alopecia and thyroid abnormalities in sheep with selenium and zinc deficiency. Five adult sheep presented marked and diffuse alopecia, and the residual hairs were dry and brittle. The skin was thick and crusty, with marked peeling. The triiodothyronine (T3) and thyroxine (T4) serum concentrations were below reference values for the species. Zinc and Se concentrations were low in both the serum and liver. During necropsy, cachexia associated with serous fat atrophy was observed, and the thyroid glands showed marked atrophy. Microscopically, the thyroid presented multifocal to coalescent atrophy, with atrophied and dilated follicles, macrophage infiltration, and the presence of fibrous connective tissue. The skin revealed hyperkeratosis and edema. It is concluded that thyroid atrophy, alopecia, and hyperkeratosis are associated with low serum and liver concentrations of zinc and selenium in sheep.

Features of the expression of Fox-1 in rat’s thyroid after prenatal dexamethasone action

The purpose of the work was to establish the features of Fox-1 expression and distribution in the parenchyma of the thyroid gland of rats in the postnatal period of ontogeny in the norm and after intrauterine action of dexamethasone.Material and methods: thyroid gland of rats (162 animals) of the Wistar line at the age from 1 to 14 days of postnatal development. Experimentally, the animals were injected intrauterinely with a solution of dexamethasone at a dose of 0.05 ml at a dilution of 1:40 on the 18th day of the dated pregnancy. The material was examined using a set of methods of morphological studies (production of histological serial sections, survey microscopy, morphometry, immunohistochemistry and statistical processing).Results of the research. In the thyroid glands of neonatal prenatal dexamethasone, the parenchyma was well developed and consisted of hollow colloid-type follicles and single colloid-type microfollicles, and a bright cytoplasmic reaction with Fox-1 antibodies was observed throughout the organ parenchyma. In the thyroid glands of animals of the 3rd day of life, morphological changes occurred in all groups of the experiment. In animals of the experimental group, hollow follicles of colloidal type of small, medium and large diameter were chaotically visualized throughout the body, and large follicles of irregular shape with immunohistochemical weak or negative reaction with Fox-1 antibodies in thyrocytes and lumen without colloidal evidence, which detected a decrease in the specific synthetic activity in these thyrocytes. On day 7 in the experimental group in the flattened thyrocytes of overstretched follicles, the expression of Fox-1 was present only in the apical part. On days 11-14 of postnatal development in the thyroid glands of rats experimentally prenatally exposed to dexamethasone in the wall of large follicles with flattened epithelium began extrafollicular proliferation of thyrocytes on the background of visualization in the lumen of these follicles desquamated cells. Intensive perinuclear and cytoplasmic Fox-1 positive reaction was present in extrafollicular proliferating thyrocytes.Conclusions. 1. The detected changes in the first day of life in the thyroid gland of rats indicated that prenatal administration of dexamethasone affects the intensification of differentiation not only structural and functional units - follicles, but also a specific synthetic intracellular apparatus of thyrocytes, judging by the intensification of Fox-1. Thus, immature pre-mRNA is converted into mature mRNA, from which thyroid proteins, in particular thyroglobulin, are translated. By the time of birth, this process in the experimental group reaches a significant development, covering the entire parenchyma of the gland. 2. In rats prenatally receiving dexamethasone, the period of lactation was characterized by intense structural changes in the thyroid gland, in particular intracellularly in thyrocytes of monolayer flattened epithelium, the expression of Fox-1 antibodies was sharply reduced, which was then replaced by a bright cytoplasmic reaction in proliferative clusters and follicles of colloidal type of secretion, which is an adaptive-compensatory mechanism of intracellular enhancement of proliferation of synthesizing organelles in response to the restructuring of a significant number of existing follicles by hypofunctional type, aimed at maintaining normal levels of thyroid function.

Radiation Dose Assessment of the Fog Lead Acrylic Shields during Coronary Angiography: A Phantom Study

This study aimed to evaluate the effects of fogging on the effectiveness of a lead glass shield in protecting an operator from radiation exposure during conventional coronary angiography (CAG). Optically stimulated luminescence dosimeters (OSLDs) were used to measure the effects of fogged lead glass shields (FLSs) and clear lead glass shields (CLSs) on the radiation doses of a cardiac catheterization surgeon. We simulated the scatter radiation incident on the operator with five angiographic projections with 10-s exposures. Experiments were conducted with a field of view of 25 cm, maximum of 100 cm between the X-ray tube and image intensifier, and 80 cm between the image intensifier and operator. Lead glass fogging had no significant effect at any angiographic projection. The average dose at the lens of the eye, thyroid glands, and gonads did not differ significantly between FLS and CLS. Although most surgeons view ceiling-suspended shields as hindrances during surgical procedures, the radiation dose at the operator’s eyes and thyroid glands increased by 13 and 10 times without the shield. The fogging of the shield is probably caused by post-surgery UV decontamination or detergents. An operator has no cause for concern regarding the radiation protection afforded by an FLS during CAG procedures.

Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers

Medullary thyroid carcinoma (MTC) accounts for only 1–2% of thyroid cancers; however, metastatic MTC is a mortal disease with no cure. In this study, glycosphingolipids were isolated from human MTCs and characterized by mass spectrometry and binding of carbohydrate recognizing ligands. The tissue distribution of selected compounds was investigated by immunohistochemistry. The amount of acid glycosphingolipids in the MTCs was higher than in the normal thyroid glands. The major acid glycosphingolipid was the GD3 ganglioside. Sulfatide and the gangliosides GM3 and GD1a were also present. The majority of the complex non-acid glycosphingolipids had type 2 (Galβ4GlcNAc) core chains, i.e., the neolactotetraosylceramide, the Lex, H type 2 and x2 pentaosylceramides, the Ley and A type 2 hexaosylceramides, and the A type 2 heptaosylceramide. There were also compounds with globo (GalαGalβ4Glc) core, i.e., globotriaosylceramide, globotetraosylceramide, the Forssman pentaosylceramide, and the Globo H hexaosylceramide. Immunohistochemistry demonstrated an extensive expression av Ley in the MTC cells and also a variable intensity and prevalence of Globo H and Lex. One individual with multiple endocrine neoplasia type 2B expressed the Forssman determinant, which is rarely found in humans. This study of human MTC glycosphingolipids identifies glycans that could serve as potential tumor-specific markers.

Electron-microscopic features of changes in the adrenal and thyroid glands in chronic hypoxia

The aim of the study was to study the characteristic features of ultrastructural changes in the cellular and extracellular matrix of the adrenal and thyroid glands in chronic hypoxia.Materials and methods. The study used the thyroid and adrenal glands of healthy adult male white rats weighing 180-200 g. The anatomical, histological, histochemical, electron microscopic and morphometric methods were used.Results. We found that the response of thyroid and adrenal cells to hypoxia is different. So, since the processes of proliferation in the cells of the thyroid gland occur faster and earlier, all tissues are restored on the 15th day of the experiment in the thyroid gland, and in the adrenal gland are restored only on the 30th day of the experiment. And this can be regarded as a higher degree of sensitivity of the adrenal glands to hypoxia, which is a stronger stress factor than the thyroid gland.Summary. The structures of the thyroid gland adapt to long-term hypoxia earlier, and responds to this with ultrastructural rearrangement – hyperplasia, hypertrophy and proliferation of thyrocytes.

Thyroid Hormones in the Human Body: A review

Thyroid gland is an essential endocrine gland that is present in the human body. This review highlights the production, regulation and disease conditions of the thyroid hormones. The thyroid gland is controlled with the help of hypothalamus and the pituitary gland that is present in the brain. The production of thyroid hormones involves five main steps such synthesis of thyroglobulin (TG), iodide uptake, iodination of thyroglobulin, storage and release. The two important hormones produced by the thyroid gland are Thyroxine (T4) and Triiodothyronine(T3). These two hormones are iodine containing derivatives. Deficiency of iodine in the body results in the reduction of T3 and T4 production. Excess and deficiency of these two hormones result in the major diseases like Hyper and Hypothyroidism. The synthetic forms of Thyroxine(T4) and Triiodothyronine(T3) used in the Pharmaceutical field are Levothyroxine and Liothyronine. Women are most commonly prone to these thyroid diseases comparatively to men. Undiagnosed disease conditions may become fatal. Levothyroxine therapy is commonly used for thyroidism which is a similar synthetic thyroid hormone. Also natural thyroid hormones that are obtained from the dried thyroid glands of animals are available. Thyroid function test and the measurement of T3, T4 plasma level becomes essential for the identification and regular maintenance of thyroid hormones in the body and human well-being.

Characterization of Glycosphingolipids in the Human Parathyroid and Thyroid Glands

As part of a systematic investigation of the glycosphingolipids in human tissues, acid and non-acid glycosphingolipids from human thyroid and parathyroid glands were isolated and characterized with mass spectrometry and binding of carbohydrate-recognizing ligands, with a focus on complex compounds. The glycosphingolipid patterns of the human parathyroid and thyroid glands were very similar. The major acid glycosphingolipids were sulfatide and the gangliosides GM3, GD3, GD1a, GD1b, GT1b and Neu5Ac-neolactotetraosylceramide, and the major non-acid glycosphingolipids were globotriaosylceramide and globoside. We also found neolactotetra- and neolactohexaosylceramide, the x2 glycosphingolipid, and complex glycosphingolipids with terminal blood group O and A determinants in both tissues. A glycosphingolipid with blood group Leb determinant was identified in the thyroid gland, and the parathyroid sample had a glycosphingolipid with terminal blood group B determinant. Immunohistochemistry demonstrated the expression of blood group A antigens in both the thyroid and parathyroid glands. A weak cytoplasmatic expression of the GD1a ganglioside was present in the thyroid, while the parathyroid gland had a strong GD1a expression on the cell surface. Thus, the glycosylation of human thyroid and parathyroid glands is more complex than previously appreciated. Our findings provide a platform for further studies of alterations of cell surface glycosphingolipids in thyroid and parathyroid cancers.