Copper,zinc, and selenium in whole blood and thyroid tissue of people with various thyroid diseases

We investigated the possible differences among the concentrations of copper, zinc, and selenium, and their mutual relations in the whole blood and thyroid tissue of patients with various thyroid disorders. Trace elements were determined by total-reflection X-ray fluorescence. The mean levels of these metals in blood as well as the mean Cu/Zn, Cu/Se, and Zn/Se ratios in the patients with thyroid cancer were significantly higher that in other patients and the control groups. However, the mean Zn and Se concentrations in the thyroid cancer tissue were significantly lower than in the thyroid tissue of other patients. In addition, the mean Cu/Zn and Cu/Se ratios in the thyroid cancer tissue were significantly higher than in the patients with other thyroid diseases. We confirm that the highest levels of copper and zinc as well as the Cu/Zn, Cu/Se, and Zn/Se ratios in the whole blood of the patients with thyroid cancer may suggest the progression of the proliferation process in the thyroid gland. We suggest that the low concentrations of zinc and selenium in the thyroid tissue confirm their participation in the carcinogenic process.     

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.     

Body, heart, thyroid gland and skeletal muscle weight changes in rats with altered thyroid status

In the present paper we describe changes of anatomical parameters in inbred Lewis strain rats, namely their body weight, body weight gain per week, absolute and relative heart, thyroid gland and skeletal muscle weights, that are assumed to reflect experimentally altered thyroid status. The hyperthyroid state was induced by DL-thyroxine or Na 3,3',5-triiodo-L-thyronine, while methimazole was employed for inducing hypothyroidism. We have found that when compared to euthyroid rats, hypothyroidism resulted in a significantly lower body weight gain, absolute and relative heart weight and, in contrast, in a significant increase of absolute and relative thyroid gland weight. On the other hand, hyperthyroidism led to a significant increase of absolute and relative heart weight and to a significant reduction of absolute and relative thyroid gland weight. However, the body mass was not significantly altered in hyperthyroidism as compared with euthyroid rats. We conclude that our protocol leads to chronic hyper- or hypothyroidism as demonstrated by body, heart and thyroid gland weight changes. These anatomical data can thus be utilized as supplemental criteria for the assessment of the thyroid state of experimental rats.     

Selenium,selenoproteins and cancer of the thyroid

Selenium is an essential mineral element with important biological functions for the whole body through incorporation into selenoproteins. This element is highly concentrated in the thyroid gland. Selenoproteins provide antioxidant protection for this tissue against the oxidative stress caused by free radicals and contribute, via iodothyronine deiodinases, to the metabolism of thyroid hormones. It is known that oxidative stress plays a major role in carcinogenesis and that in recent decades there has been an increase in the incidence of thyroid cancer. The anti-carcinogenic action of selenium, although not fully understood, is mainly attributable to selenoproteins antioxidant properties, and to the ability to modulate cell proliferation (cell cycle and apoptosis), energy metabolism, and cellular immune response, significantly altered during tumorigenesis. Researchers have suggested that different forms of selenium supplementation may be beneficial in the prevention and treatment of thyroid cancer; however, the studies have several methodological limitations. This review is a summary of the current knowledge on how selenium and selenoproteins related to thyroid cancer.     

Dimethylsulfoxide maintains human thyroid cells in suspension culture, facilitating synthesis and release of thyroid hormone

Usually, human thyrocytes in primary culture rapidly lose their thyroid function and fail to synthesize or release thyroid hormone after 3-5 days of culture. By culturing thyroid follicles obtained from patients with Graves' disease in medium supplemented with TSH and a low concentration of fetal calf serum (1%), thyrocytes can maintain thyroid function for several days. We have found that the addition of dimethylsulfoxide to culture medium (1.7%) furthermore enhanced and maintained thyroid function (de novo synthesis and release of [125I] thyroxine) for more than 13 days, probably by inhibiting dedifferentiation of thyrocytes. The present bioassay will be also useful for detecting thyroid stimulating immunoglobulin in patients with Graves' disease.     

Leydig cells, thyroid hormones and steroidogenesis

Leydig cells are the primary source of androgens in the mammalian testis. It is established that the luteinizing hormone (LH) produced by the anterior pituitary is required to maintain the structure and function of the Leydig cells in the postnatal testis. Until recent years, a role by the thyroid hormones on Leydig cells was not documented. It is evident now that thyroid hormones perform many functions in Leydig cells. For the process of postnatal Leydig cell differentiation, thyroid hormones are crucial. Thyroid hormones acutely stimulate Leydig cell steroidogenesis. Thyroid hormones cause proliferation of the cytoplasmic organelle peroxisome and stimulate the production of steroidogenic acute regulatory protein (StAR) and StAR mRNA in Leydig cells; both peroxisomes and StAR are linked with the transport of cholesterol, the obligatory intermediate in steroid hormone biosynthesis, into mitochondria. The presence of thyroid hormone receptors in Leydig cells and other cell types of the Leydig lineage is an issue that needs to be fully addressed in future studies. As thyroid hormones regulate many functions of Sertoli cells and the Sertoli cells regulate certain functions of Leydig cells, effects of thyroid hormones on Leydig cells mediated via the Sertoli cells are also reviewed in this paper. Additionally, out of all cell types in the testis, the thyrotropin releasing hormone (TRH), TRH mRNA and TRH receptor are present exclusively in Leydig cells. However, whether Leydig cells have a regulatory role on the hypothalamo-pituitary-thyroid axis is currently unknown.     

The mRNA levels of thyrotropin receptor, thyroglobulin and thyroid peroxidase in neoplastic human thyroid tissues

Expression levels of thyrotropin receptor (TSH-R), thyroglobulin (Tg) and thyroid peroxidase (TPO) mRNA in normal and neoplastic human thyroid tissues (6 adenomas and 7 carcinomas) were investigated by Northern-blot and slot-blot analyses. We found that TSH-R mRNA levels were significantly lower in carcinoma tissues than in normal tissues. The levels of Tg mRNA were also significantly lowered in adenoma and carcinoma tissues as compared to normal tissues. In contrast, no significant difference was observed in the expression levels of TPO mRNA between these tissues. Furthermore, TSH-R mRNA levels were well-correlated with Tg mRNA levels in neoplastic tissues. These results suggest that mRNAs of TSH-R and Tg are expressed in relation to their degree of differentiation.     

Characterization, purification, and subcellular localization of bovine thyroid sialidases

Sialidase activities have been studied in bovine thyroid using sialoglycolipids, sialoglycoproteins, sialo-oligosaccharides and fluorogenic 4-methylumbelliferyl-alpha-D-N-acetylneuraminate as substrates. No sialidase activity could be detected towards native glycoprotein substrates. From enzyme kinetics, effector data and more convincingly from subcellular studies it became clear that in bovine thyroid at least two sialidase activities were present, a sialyllactitol sialidase confined to the lysosomal membrane and a glycolipid sialidase residing in the plasma membrane and displaying the features of a true ectoenzyme. The lipid requirement for full enzyme activity supported the membrane bound character of both sialidase activities. A soluble sialidase activity could not be demonstrated. After solubilization by CHAPS treatment, partial purification of the sialyllactitol sialidase could be achieved by affinity chromatography (Sepharose diamino dipropylamino-N-acetylneuraminic acid). The purified enzyme was extremely labile. Titration of the sialidase preparation with amino acid modifying agents revealed that sulfhydryl- and tryptophanyl groups were essential for the sialidase action.     

Maternal thyroid disease,thyroid medication use,and selected birth defects in the National Birth Defects Prevention Study

BACKGROUND: Although thyroid disorders are present in approximately 3% of pregnant women, little is known about the association between maternal thyroid disease and birth defects. METHODS: We assessed the association between maternal thyroid disease, thyroid medication use, and 38 types of birth defects among 14,067 cases and 5875 controls in the National Birth Defects Prevention Study, a multisite, population‐based, case‐control study. Infants in this study were born between October 1997 and December 2004. Information on exposures including maternal diseases and use of medications was collected by telephone interview. RESULTS: We found statistically significant associations between maternal thyroid disease and left ventricular outflow tract obstruction heart defects (1.5; 95% CI, 1.0–2.3), hydrocephaly (2.9; 95% CI, 1.6–5.2), hypospadias (1.6; 95% CI, 1.0–2.5), and isolated anorectal atresia (2.4; 95% CI, 1.2–4.6). Estimates for the association between periconceptional use of thyroxine and specific types of birth defects were similar to estimates for any thyroid disease. Given that antithyroid medication use was rare, we could not adequately assess risks for their use for most case groups. CONCLUSIONS: Our results are consistent with the positive associations between maternal thyroid disease or thyroid medication use and both hydrocephaly and hypospadias observed in some previous studies. New associations with left ventricular outflow tract obstruction heart defects and anorectal atresia may be chance findings. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Selenium,zinc, and thyroid hormones in healthy subjects

Iodothyronine 5′ deiodinase, which is mainly responsible for peripheral T₃ production, has recently been demonstrated to be a selenium (Se)-containing enzyme. The structure of nuclear thyroid hormone receptors contains Zinc (Zn) ions, crucial for the functional properties of the protein. In the elderly, reduced peripheral conversion of T₄ to T₃ with a lower T₃/T₄ ratio and overt hypothyroidism are frequently observed. We measured serum Se and RBC GSH-Px (as indices of Se status), circulating and RBC Zinc (as indices of Zn status), thyroid hormones and TSH in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to avoid abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid under- or malnutrition conditions, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. Low T₃/T₄ ratios and reduced Se and RBC GSH-Px activity were observed only in the older group. A highly significant linear correlation between the T₃/T₄ ratio and indices of Se status was observed in the older group of subjects (r=0.54;p<0.002, for Se;r=0.50;p<0.002, for RBC GSH-Px). Indices of Zn status did not correlate with thyroid hormones, but RBC Zn was decreased in older as compared with younger subjects. We concluded that reduced peripheral T₄ conversion is related to impaired Se status in the elderly.     

Adenosine, thyroid status and regulation of lipolysis.

We have previously observed that, on subcutaneous administration, a significant proportion of insulin is degraded at the site of injection. The present paper reports that the degradative activity of slices of rat adipose tissue can be inhibited in vitro by ophthalmic acid, a natural analogue of glutathione, and by bovine pancreatic proteinase inhibitor, whereas it is increased by the addition of reduced glutathione.     

Purification of cytosolic,latent endoribonuclease from porcine thyroid

An alkaline endoribonuclease was purified 1800-fold from the cytosolic, latent ribonuclease fraction of porcine thyroids by gentle procedures specifically designed to exclude both heating and acidification steps. Polyacrylamide gel electrophoresis revealed a broad peak of enzyme activity that was coincident with the stained protein band. As estimated by gel filtration chromatography the major form of the enzyme (59%) had a molecular weight of 51,000; the remainder of the activity was distributed among six minor forms. Carboxymethyl-cellulose chromatography showed that the enzyme had at least three interconvertible forms. The latent alkaline ribonuclease had a pH optimum of 8.1 in both Tris and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffers and was stimulated by a number of monovalent chloride and potassium salts at ionic strengths between 10 and 70 mm; above 100 mm the salts were all inhibitory with the exception of ammonium chloride. At 1 mm both MgCl₂ and CaCl₂ were stimulatory, whereas CuCl₂ ZnCl₂ and EDTA were inhibitors. Both native and denatured DNA were slightly stimulatory. The porcine thyroid latent alkaline ribonuclease was specific for pyrimidine homopolymers and yielded a mixture of cyclic mononucleotides and oligonucleotides when incubated with poly(C). It did not hydrolyze 2′(3′)-cyclic CMP, purine homopolymers, native or denatured DNA or poly(A) · poly(U). Its activity toward rRNA was greater than toward tRNA and it cleaved the former to a mixture of mononucleotides and oligonucleotides. The properties of the intracellular, cytosolic, latent, alkaline ribonuclease distinguish it from pancreatic ribonuclease A and other nonsecretory ribonucleases.     

A novel thyroid hormone receptor-beta mutation,not anticipated to occur in resistance to thyroid hormone,causes variable phenotypes

Resistance to thyroid hormones (RTH) is a syndrome characterized by a variable tissue hyposensitivity to thyroid hormones and is linked to mutations in the thyroid hormone receptor-beta (TRbeta) gene. We report here for the first time in vivo the mutation R429W (CCG-->TCG) located in the exon 10. The artificial mutant obtained in vitro displayed a normal T(3)-binding affinity and transactivation function. Therefore, it was thought to produce little, if any, clinical effect and to escape to clinical detection. The present report is at least in part discordant with this prediction since the propositus and his grandmother had an authentic hyperthyroidism with high FT(4) plasma level in the presence of inappropriate TSH. On the other hand, spontaneous variations of clinical features and - interestingly - of plasma FT(4) concentrations with time in the propositus, and the phenotype observed in his mother who never complained with thyrotoxic symptoms, confirmed the in vitro binding and functional predictions. The most intriguing is the clinical course of the grandmother as she first presented with predominant pituitary RTH and a diffuse goiter and finally with a toxic multinodular goiter with normal T(3) and T(4) plasma concentrations and suppressed TSH. In conclusion, we report a novel mutation in the gene encoding the thyroid hormone receptor responsible for predominant pituitary RTH already described in vitro but not in vivo. The fluctuant phenotype of the propositus suggests that other factors modulate the degree of tissue resistance that is under genetic control. Toxic multinodular goiter, possibly due to chronic TSH stimulation during RTH, in addition to the phenotype variability, increases the difficulty to diagnose this thyroid disorder.     

Roles of thyroid, adrenal and pancreatic hormones on thyroid activity of the soft-shelled turtles Lissemys punctata punctata Bonnoterre

The effects of some exogenous peripheral hormones (thyroxine, corticosterone, epinephrine, norepinephrine and insulin) on thyroid activity were investigated in juvenile female soft-shelled turtles, Lissemys punctata punctata. Each hormone was injected in three different doses (25 microg, 50 microg or 100 microg each per 100 g body weight, once daily at 9 AM) for 10 consecutive days. Thyroid activity was evaluated by gravimetry, histology (epithelial height) and thyroperoxidase assay. The findings revealed that thyroxine in low dose (25 microg) stimulated thyroid activity by increasing the relative thyroid weight, epithelial height and thyroperoxidase activity, but inhibited gland activity at a high dose (100 microg) by decreasing the values of all these parameters. The medium dose (50 microg) had no significant effect. All other hormones, in all doses, significantly decreased thyroid activity by decreasing the values of all the parameters. Thyroid responses to exogenous hormones are generally dose-dependent in turtles. The mechanisms of actions of the hormones administered are suggested.