Effect of arginine-vasopressin on the rat thyroid gland in vitro

The response of the rat thyroid gland to arginine-vasopressin in vitro was studied to clear a possibility of a direct regulation of this gland by hypothalamic nonapeptide neurohormones. The function of the thyroid gland was estimated by thyrocyte height and quantity of the autoradiographs on a thyrocyte. AVP makes more active hormone synthesis in thyrocytes after 30 min of incubation and it stimulates both synthesis and secretion of the thyroid hormones in 2 hours of incubation. The higher concentrations of AVP activate the thyroid hormone synthesis but not the secretion.     

Histological and ultrastructural alterations of rat thyroid gland after short-term treatment with high doses of thyroid hormones

The aim of the present study was to investigate histological alterations of rat thyroid gland after short-term treatment with supraphysiological doses of thyroid hormones. Rats from experimental groups were treated with triiodothyronine (T3) or thyroxine (T4) during five days. In both treated groups, thyrocyte height was reduced and follicular lumens were distended. Progressive involutive changes of the thyroid parenchyma were apparent, including follicular remodeling (fusion) and death of thyrocytes. Morphological changes confirmed by quantitative analysis were more pronounced in the T4-treated group. Our results demonstrate that thyrotoxicosis, whether induced by T3 or T4, leads to different grades of thyroid tissue injury, including some irreversible damages. These changes might be explained at least in part by lack of trophic and cytoprotective effects of the thyroid stimulating hormone. Since the period required for morphophysiological recovery may be unpredictable, findings presented here should be taken into consideration in cases where the thyroid hormones are used as a treatment for thyroid and non-thyroid related conditions.     

Determination of thyroxine and triiodothyronine in the thyroid glands of encephalectomized rat fetuses

Concentration of thyroxin and triiodothyronine in the thyroid gland of encephalectomized and intact fetuses of rats with normal and prolonged gestation period was determined by means of isotope methods. Encephalectomy of 19-day old fetuses did not produce any significant effect on the concentration of thyroid hormones in the gland 2 and 4 days after the operation. The results obtained pointed to the absence of the hypothalamic control over the thyroid function in prenatal development of rats.     

Interaction of thyroid hormones and cortisol on binding proteins of cytosol and nuclear extract of human leukocytes

Competitive properties of thyroid hormone analogues and cortisol for the binding of triiodothyronine and thyroxine, expressed as apparent inhibition constants (Ki), have been measured in nuclear extract and cytosol proteins of human leukocytes by means of electrophoresis in polyacrylamide gradient gel and charcoal-dextran assay. In the cytosol not only thyroid hormones but also cortisol competed for the binding of triiodothyronine and thyroxine as tested by charcoal-dextran assay. By means of electrophoresis two protein fractions binding thyroid hormones were found: protein fraction designed A (m. w. 100,000) and protein fraction B (m. w. 83,000). In protein fraction A the inhibition constant Ki for thyroid hormones are lower than in protein fraction B. In the protein fraction B not only thyroid hormones but also cortisol competed for the binding of triiodothyronine and thyroxine. In the nuclear extract the thyroid hormones were bound in one protein fraction C (m. w. 58,000) only. In this protein fraction only thyroid hormones, but not cortisol, are competitors for the binding of triiodothyronine and thyroxine and in the following descending order: triiodothyronine, thyroxine, tetraiodothyroacetic acid, thyroxamine and D-thyroxine. The competition of cortisol for the binding of thyroid hormones in cytosol protein fraction B in connection with some serum TBG changes in patients after prednisone administration is discussed.     

Stress and the thyroid gland

The review highlights the effects of acute and chronic stress on thyroid gland metabolism. Special attention is paid to the influence of stress and the direct effects of glucocorticoids on the thyroid status, the activities of thyrocytes, iodine uptake, its oxidation and organification as well as peripheral metabolism of thyroid hormones (deposition and transport of thyroid hormones, deiodinase activities in different tissues). The role of stress in the development of thyroid pathology is analyzed and characteristic features of thyroid function alterations during impaired functioning of the pituitary-adrenal system are established. Taking into consideration serious consequences of thyroid deficiency for the body, even in subclinical thyroid insufficiency, the mechanisms of the stress-induced impairments in thyroid functions are of interest for further studies.     

State of the rat thyroid gland in coarctation of the abdominal aorta]

In order to study connections between blood vessels and follicular thyrocytes, the method of modulation (a purposeful change of state in one element with registration of states in other elements of the system) was used. In rats chronic increase of blood stream was produced in the thyroid gland; in 15 days it was 54% as high as in the control. The volume of the vascular bed increased by 28% and that of follicles by 26%. Volumetric ratio between the thyroid epithelium and colloid did not changed. Follicular thyrocytes grew high and the nuclear volumes of these cells increased. Thyrocytes greately varied in their height. The number of mast cells in the thyroid gland remained the same. Iodine absorption by the thyroid gland increased as it is dependent on the volume of the vascular bed of the organism (+0.82). The data obtained demonstrate a significant connection existing between the follicular thyrocytes and blood vessels.     

A role of thyroid hormones in differentiation of mouse mammary gland in vitro.

Addition of thyroxine or triiodothyronine to cultures of mammary gland explants in the presence of insulin, hydrocortisone and prolactin, results in a selective enhancement of the activity of the milk protein, α-lactalbumin. This effect, which is specific for the L-isomer of the thyroid hormones, is not mediated through diffusible activators of the enzyme activity.     

Structure of the thyroid gland, serum thyroid hormones, and the reproductive cycle of the Atlantic stingray, Dasyatis sabina.

This study examines the role of the thyroid gland in the control of reproduction in the viviparous Atlantic stingray, Dasyatis sabina. Thyroid activity in individuals in different reproductive stages was assessed both by microscopic examination of the gland, and by analysis of circulating levels of thyroid hormones from the same individuals. The thyroid gland is a cylindric organ, embedded in a connective tissue capsule, and composed of follicles, i.e., monolayer spheres of thyroid epithelial cells. Stingray follicular cells possess several characteristic features, namely apical cilia and a well-developed endoplasmic reticulum. Cells vary in size and shape, according to the activity of the gland. No structural differences were observed between the thyroid glands of the two sexes. Both thyroid hormones, triiodothyronine, [T(3)], and thyroxine, [T(4)], were detected in the serum of all animals examined. Levels ranged from 1.3-2.6 microg/100 ml for total T(4), and from 1.2-2.6 ng/ml for total T(3). The T(4) levels did not vary significantly in any group. Immature individuals and females undergoing oogenesis had the lowest levels of circulating T(3) and mature females from ovulation throughout gestation had high thyroid gland activity and high levels of circulating T(3). J. Exp. Zool. 284:505-516, 1999.     

Iodine-containing hormones--dipole modifiers of phospholipid membranes

The hormones of thyroid gland thyroxine and triiodothyronine were shown to increase the permeability of bilayer lipid membrane (BLM) and inner mitochondrial membrane for hydrophobic positively charged complex K+-nonactine and to decrease the permeability of these membranes for hydrophobic anion FCCP-. These facts imply that the thyroid hormones affect the phospholipid membranes like the dipole modifyers decreasing the positive potential of hydrophobic region of the membranes in respect to the water phase.     

Calpain inhibitors regulate the conversion of thyroid gland follicles in rats and humans

Effects of calpain inhibitors on thyroid follicle conversion into monolayer was investigated. Human and rat primary thyroid cultures require the follicular structure after enzyme disaggregation of native tissue fragments. Removal of thyroid-stimulating hormone (TSH) from the culture medium causes migration of thyrocytes from follicles into monolayer, some differences were noted in conversion of rat and human thyroid follicles. The locomotion of rat thyrocytes is observed after preliminary incubation with TSH, but migration of thyrocytes from human thyroid follicles does not require such a preincubation. Phorbol esters induce migration of rat and human thyroid cells. Calpain inhibitors exert a significant influence on locomotion of the thyroid gland cells induced by the removal of TSH from the culture medium. Human thyrocyte migration is markedly inhibited by calpain inhibitor I or II. Likewise, addition of calpain inhibitor I into primary culture of rat thyrocytes decreased the number of migrating cells by 52%, and shortened average migration distance by 34%. Also, calpain inhibitors reduced the speed of phorbol ether-induced conversion of rat and human thyroid follicles into monolayer.     

Seasonal changes in circulating levels of thyroid hormones are not dependent on the age in Djungarian hamsters Phodopus sungorus

1. Plasma levels of total and free thyroxine (T4; FT4) and triiodothyronine (T3; FT3) were measured by radioimmunoassay in adult and senescent Djungarian hamsters at different times of the year. 2. Seasonal changes of both hormones were found in adult and senescent hamsters. 3. However, except for total thyroxine, the patterns were different in both groups of hamsters. 4. These results suggest, that in Djungarian hamsters age-related changes of thyroid function do not affect the secretory activity of the thyroid gland rather than the phase of the seasonal cycle.     

Role of megalin (gp330) in transcytosis of thyroglobulin by thyroid cells. A novel function in the control of thyroid hormone release

When thyroglobulin (Tg) is endocytosed by thyrocytes and transported to lysosomes, thyroid hormones (T4 and T3) are released. However, some internalized Tg is transcytosed intact into the bloodstream, thereby avoiding proteolytic cleavage. Here we show that megalin (gp330), a Tg receptor on thyroid cells, plays a role in Tg transcytosis. Following incubation with exogenous rat Tg at 37 degrees C, Fisher rat thyroid (FRTL-5) cells, a differentiated thyroid cell line, released T3 into the medium. However, when cells were incubated with Tg plus either of two megalin competitors, T3 release was increased, suggesting that Tg internalized by megalin bypassed the lysosomal pathway, possibly with release of undegraded Tg from cells. To assess this possibility, we performed experiments in which FRTL-5 cells were incubated with either unlabeled or (125)I-labeled Tg at 37 degrees C to allow internalization, treated with heparin to remove cell surface-bound Tg, and further incubated at 37 degrees C to allow Tg release. Intact 330-kDa Tg was released into the medium, and the amount released was markedly reduced by megalin competitors. To investigate whether Tg release resulted from transcytosis, we studied FRTL-5 cells cultured as polarized layers with tight junctions on permeable filters in the upper chamber of dual chambered devices. Following the addition of Tg to the upper chamber and incubation at 37 degrees C, intact 330-kDa Tg was found in fluids collected from the lower chamber. The amount recovered was markedly reduced by megalin competitors, indicating that megalin mediates Tg transcytosis. We also studied Tg transcytosis in vivo, using a rat model of goiter induced by aminotriazole, in which increased release of thyrotropin induces massive colloid endocytosis. This was associated with increased megalin expression on thyrocytes and increased serum Tg levels, with reduced serum T3 levels, supporting the conclusion that megalin mediates Tg transcytosis. Tg transcytosis is a novel function of megalin, which usually transports ligands to lysosomes. Megalin-mediated transcytosis may regulate the extent of thyroid hormone release.     

Physiological and Morphological Specific Features of the Formation of the Thyroid Status in the Aboriginal and Migrant Populations of Magadan Oblast

Ultrasonographic determinations of the thyroid gland volumes and measurement of the blood plasma content of thyroxin and triiodothyronine were carried out in 1176 apparently healthy residents of the Magadan oblast, all those examined being divided by sex, age, and the adaptation time in the North. Special attention was given to the thyroid system parameters of the aborigines 17 to 40 years old living in the urban area and not involved in the traditional life style. The indigenous population of the Extreme North and migrants were shown to have marked functional adaptive hyperplasia of the thyroid gland and diffuse goiter in 15% of cases. The size of the thyroid gland and the level of the thyroid hormones in the aboriginal population are within the average European range. Diffuse goiter manifestations in males virtually do not occur; in women, the incidence does not exceed 5%. The assumption is advanced as to the formation in aborigines of the northern hypothyroid phenotype providing for the sustained optimal level of the thyroid system functioning without an increase in the thyroid volume.     

Selective enrichment of phytosphingosine in glycosphingolipids of isolated human thyrocytes as compared to the whole thyroid

The glycosphingolipids of isolated human thyrocytes have been analyzed. As compared to the total thyroid gland, the pattern of gangliosides was found to be similar, whereas the neutral glycolipid profile was quite different, with glucosylceramide as the major glycosphingolipid of thyrocytes. Moreover, this glucosylceramide contains almost exclusively phytosphingosine (4-D-hydroxy-sphinganine) which is only a minor component in the long-chain bases of the glycosphingolipids extracted from the whole thyroid gland.     

Histochemical studies of several "K"-cell enzymes in guinea pig thyroid glands]

The thyroid gland of guinea pigs were studied morphologically. Histochemical methods were used for detection of lactate dehydrogenase, succinic dehydrogenase, cholinesterase, alkaline phosphatase and acid phosphatase. The distribution of "C"-cells in normal thyroid glands was proved to be uneven. In the center of the gland they were more numerous. For statistical investigations the method of silver impregnation of "C"-cells is more practicable, since they can not be obviously distinguished from acinar cells on the basis of glycerophosphate dehydrogenase only. The activity of cholinestarase in "C"-cells and in some other cells of folliculi epithelium is very high. A supposition is made that there exist two kinds of the follicular lining thyrocytes, having different histochemical properties and histogenesis as well.     

The trace element selenium and the thyroid gland.

Apart from the essential trace element iodine, which is the central constituent of thyroid hormones, a second essential trace element, selenium, is required for appropriate thyroid hormone synthesis, activation and metabolism. The human thyroid gland has the highest selenium content per gram of tissue among all organs. Several selenocysteine-containing proteins respectively enzymes are functionally expressed in the thyroid, mainly in thyrocytes themselves: three forms of glutathione peroxidases (cGPx, pGPx, and PH-GPx), the type I 5-deiodinase, thioredoxin reductase and selenoprotein P. The thyroidal expression of type II 5-deiodinase still is controversial. As thyrocytes produce H2O2 continuously throughout life an effective cell defense system against H2O2 and reactive oxygen intermediates derived thereof is essential for maintenance of normal thyroid function and protection of the gland. In experimental animal models long-term and strong selenium deficiency leads to necrosis and fibrosis after high iodide loads. Combined iodide and selenium deficiency such as in central Zaire is thought to cause the myxedematous form of endemic cretinism. Inadequate selenium supply and prediagnostically low serum selenium levels are significantly correlated with the development of thyroid carcinoma and other tumors. Though selenium supply controls expression and translation of selenocysteine-containing proteins no direct correlation is found between selenium tissue content and expression of various thyroidal selenoproteins, indicating that other regulatory factors contribute to or override selenium-dependent expression control, e.g., in thyroid adenoma, carcinoma or autoimmune disease. As both trace elements, iodine and selenium, were washed out from the upper layers of the soil during and after the ice ages in many regions of the world adequate supply with these essential compounds needs to be provided either by a balanced diet or supplementation.     

Molecular Mechanisms of the Relationship between Thyroid Dysfunctions and Diabetes Mellitus

Type 1 and type 2 diabetes mellitus (DM) are known to increase the incidence of thyroid gland (TG) dysfunctions. The review addresses the literature data and our experimental results on the molecular mechanisms that underlie thyroid disorders under DM. Most important of these mechanisms are the attenuation of thyrocyte adenylyl cyclase signaling system sensitivity to thyroid-stimulating hormone, the decrease in the number of thyroid hormone receptors in peripheral tissues, and the decline in activity as well as changes in the ratio of different deiodinase forms in these tissues. Decreased activity of D2 deiodinases, which convert thyroxine into the active form of triiodothyronine, is associated with the development of insulin resistance, while decreased activity of D3 deiodinases, which catalyze inactivation of triiodothyronine in pancreatic β cells, suppresses insulin secretion and leads to insulin deficiency. Thus, both the excess and the deficiency of thyroid hormones can entail diabetic pathology. Identification of thyroid disorders is of utmost importance for elaborating novel approaches to treat and prevent thyroid diseases associated with type 1 and type 2 DM.     

Action of lysosomotropic modulators on the thyroid cells of rats

Hydrocortisone, ammonium chloride, pepstatin and contrykal have been studied for their effect on incubated and cultured fragments of rat thyroid gland. It is found that the radioactive iodine uptake by thyroid gland cells is inhibited by hydrocortisone, ammonium chloride and pepstatin. Pepstatin induces formation of vacuoles with nonhydrolyzed thyroglobulin in thyrocytes.