Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

INTRODUCTION: Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. OBJECTIVE: The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. DESIGN AND METHODS: The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. RESULTS: LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. CONCLUSIONS: In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours.

Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.

The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood.

Androgen receptor expression in human thyroid cancer tissues: a potential mechanism underlying the gender bias in the incidence of thyroid cancers.

Gender bias in the incidence of thyroid cancer is well known, however, the underlying mechanism is largely unknown. The current study determines variations in the molecular characteristics of thyroid cancers between men and women. Normal and cancerous thyroid tissues were collected from a total of 125 men and women who underwent surgical thyroidectomy. Testosterone levels in serum and thyroid cancer tissues were elevated in women while it decreased in men compared to respective control groups; whereas, ligand binding activity increased in men and decreased in women. Androgen receptor (AR) mRNA expression increased in a majority of men while it decreased in a majority of women except those with follicular thyroid carcinoma (FTC). In thyroid cancers of women, Pearson's correlation analysis showed a positive correlation of AR mRNA with AR protein, CBP and Sp1, whereas AR mRNA showed a negative correlation with p53. In case of men, AR mRNA showed a positive correlation with AR and cyclin D1 proteins in papillary thyroid carcinoma (PTC); and CBP and Sp1 in follicular thyroid adenoma (FTA), whereas AR mRNA showed a positive correlation with p53. Our study identified for the first time that AR is posttranscriptionally regulated by miR-124a in thyroid cancer tissues. Further, our in vitro studies with a PTC cell line (NPA-87-1) showed miR-124a as the potent inhibitor of AR that impairs cell proliferation even in the presence of testosterone. Thus, the current study suggests that: (i) the varying pattern of testosterone level and AR status in thyroid tissues of men and women may predispose to the gender specific incidence of thyroid tumors and (ii) miR-124a plays a significant role in determining the AR gene expression pattern and thus, androgen mediated thyroid tumor growth.