Behavioural alterations provoked by prolonged calcitonin administration in rats

Present work investigated the effect of prolonged administration of salmon calcitonin, a hormone secreted by parafollicular cells from thyroid, on behavioural parameters of rats. Animals received calcitonin sc, 100 mUI/100 g of body weight, three times a week, during 50 days. Behaviour was assessed utilizing an Open Field, Elevated Plus-Maze and Hole Board apparatus. Calcitonin treatment in rats seems to modify open field and elevated plus maze behaviour, suggesting emotionality and anxiety state alterations of the animals. These conditions can be provoked due to the direct calcitonin action on its receptors, even though we do not exclude an action mediated by tissue calcium level alterations.

Localization of myosin-Va in subpopulations of cells in rat endocrine organs

Myosin-Va is a Ca 2+/calmodulin-regulated unconventional myosin involved in the transport of vesicles, membranous organelles, and macromolecular complexes composed of proteins and mRNA. The cellular localization of myosin-Va has been described in great detail in several vertebrate cell types, including neurons, melanocytes, lymphocytes, auditory tissues, and a number of cultured cells. Here, we provide an immunohistochemical view of the tissue distribution of myosin-Va in the major endocrine organs. Myosin-Va is highly expressed in the pineal and pituitary glands and in specific cell populations of other endocrine glands, especially the parafollicular cells of the thyroid, the principal cells of the parathyroid, the islets of Langerhans of the pancreas, the chromaffin cells of the adrenal medulla, and a subpopulation of interstitial testicular cells. Weak to moderate staining has been detected in steroidogenic cells of the adrenal cortex, ovary, and Leydig cells. Myosin-Va has also been localized to non-endocrine cells, such as the germ cells of the seminiferous epithelium and maturing oocytes and in the intercalated ducts of the exocrine pancreas. These data provide the first systematic description of myosin-Va localization in the major endocrine organs of rat. © 2008 Springer-Verlag.

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Thyroid cell proliferation in Graves' disease - Use of MIB-1 monoclonal antibody

OBJECTIVE: To measure thyroid cell proliferation in patients with Graves' disease (GD) before and during treatment with antithyroid drugs.STUDY DESIGN: Patients were assessed by fine needle aspiration biopsy before (n=20) and after 4 (n=19) and 12 months of treatment (n=15) with propylthiouracil or methimazole. Cell proliferation index (CPI) was estimated by immunocytochemistry using MIB-1. CPI was studied in relation to the cytologic parameters of the smears; clinical parameters, such as Wayne's Clinical Index (WCI) and time without treatment; laboratory parameters, such as (131)Iuptake and dosage of serum free thyroxin and thyroid-stimulating hormone; and thyroid ultrasound.RESULTS: CPI varied from 0.00% to 25.00% before treatment, 0.00% to 23.00% at 4 months and 0.00% to 14.84% at 12 months. CPI median values were 6.50%, 4.30% and 3.30%, respectively (before and after 4 months and 12 months of treatment). CPI had a positive correlation with WCI and FT4 at 12 months of treatment.CONCLUSION: Thyroid CPI in GD varies from case to case. However, due to its decreasing pattern during follow-up and its positive correlation with thyrotoxicosis severity, CPI may indicate the functional status of the gland and contribute to a better understanding of GD.

Influence of estradiol and triiodothyronine on breast cancer cell lines proliferation and expression of estrogen and thyroid hormone receptors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Primary squamous cell carcinoma of the thyroid diagnosed as anaplastic carcinoma: failure in fine-needle aspiration cytology?

A case of primary squamous-cell carcinoma (SCC) of the thyroid which had been initially diagnosed as an anaplastic carcinoma (ATC) is described: female, 73 years old, with a fast-growing cervical nodule on the left side and hoarseness for 3 months. Ultrasonography showed a 4.5 cm solid nodule. FNA was compatible with poorly differentiated carcinoma with immunoreactivity for AE1/AE3, EMA. Thyroidectomy was performed. Histopathological examination showed a nonencapsulated tumor. Immunohistochemistry disclosed positivity for AE1/AE3, p53,p63, and Ki67. The diagnosis was ATC. A second opinion reported tumor consisting of squamous cells, with intense inflammatory infiltrate both in tumor and in the adjacent thyroid, with final diagnosis of SCC, associated with Hashimoto thyroiditis. No other primary focus of SCC was found. Patient has shown a 48-month survival period. Clinically, primary SCCs of the thyroid and ATCs are similar. The distinction is often difficult particularly when based on the cytological analysis of FNA material.

Somatotrophic and thyroid hormones around the onset of lay in broiler breeders under different conditions

Somatotrophic and thyroid hormones were determined around the onset of reproduction in broiler breeders reared in two different housing systems [dark, close-sided house (CH) and conventional, open-sided house (OH)]. In both groups age-related changes were obvious for thyroxine (T-4), growth hormone (GH) and insulin-like growth factor (IGF-1); levels of T-4 decreased, especially between 24 and 28 weeks in both groups; concomitantly GH sharply increased over the same period. A transient peak in triiodothyronine (T-3) occurred between 25 and 27 weeks. The effect of housing was only present after the onset of lay. Between weeks 27-28 and the end of the period studied, the CH group showed higher levels of GH and T-3 but lower T-4 levels as compared to the OH group. A significant increase in GH after onset of lay, without any significant rise in T-3 or in IGF-I, could point to a relative insensitivity to high plasma GH levels. Changes at GH receptor level, together with an increased pituitary GH secretion and/or decreased GH turnover may be expected. This may indicate that hypothalamo-pituitary changes at the onset of lay not only imply changes of gonadotrophic cell function, but also other hormonal axes. The relatively decrease in T-4 without changes in T-3, may point to a decrease in the activity of the thyrotropic axis.

Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure.

Effect of thyroid hormone T3 on Myosin-Va expression in the central nervous system

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Profile of thyroid hormones in breast cancer patients

Estrogen involvement in breast cancer has been established; however, the association between breast cancer and thyroid diseases is controversial. Estrogen-like effects of thyroid hormone on breast cancer cell growth in culture have been reported. The objective of the present study was to determine the profile of thyroid hormones in breast cancer patients. Serum aliquots from 26 patients with breast cancer ranging in age from 30 to 85 years and age-matched normal controls (N = 22) were analyzed for free triiodothyronine (T3F), free thyroxine (T4F), thyroid-stimulating hormone (TSH), antiperoxidase antibody (TPO), and estradiol (E2). Estrogen receptor ß (ERß) was determined in tumor tissues by immunohistochemistry. Thyroid disease incidence was higher in patients than in controls (58 vs 18%, P < 0.05). Subclinical hyperthyroidism was the most frequent disorder in patients (31%); hypothyroidism (8%) and positive anti-TPO antibodies (19%) were also found. Subclinical hypothyroidism was the only dysfunction (18%) found in controls. Hyperthyroidism was associated with postmenopausal patients, as shown by significantly higher mean T3 and T4 values and lower TSH levels in this group of breast cancer patients than in controls. The majority of positive ERß tumors were clustered in the postmenopausal patients and all cases presenting subclinical hyperthyroidism in this subgroup concomitantly exhibited Erß-positive tumors. Subclinical hyperthyroidism was present in only one of 6 premenopausal patients. We show here that postmenopausal breast cancer patients have a significantly increased thyroid hormone/E2 ratio (P < 0.05), suggesting a possible tumor growth-promoting effect caused by this misbalance.

Triiodothyronine mimics the effects of estrogen in breast cancer cell lines

MCF-7 (estrogen receptor positive - ER(+)) and MDA-MB-231 (estrogen receptor negative - ER(-)) are human breast cancer cell lines which express functional thyroid hormone receptors (c-erb A alpha 1 and c-erb beta 1) as indicated by stimulation of mitochondrial alpha-glycerophosphate dehydrogenase. In MCF-7, mimicking E(2), T-3 stimulated growth in a dose-dependent (10(10) M-10(-8) M) manner, induced the expression of progesterone receptor and growth factor TGF alpha mRNAs and inhibited that of TGF beta mRNA; T-3 also increased progesterone binding and LDH5 isozyme activities. None of these effects were observed in (ER(-)) MDA-MB-231 cells. 10(-6) M tamoxifen (TAM) reverted growth stimulation, suppressed progesterone receptor and TGF alpha mRNA induction and restored TGF beta mRNA to control levels in T-3-treated MCF-7 cells. That T-3 is acting in MCF-7 cells via its binding to ER is suggested by the immunoprecipitation of pre-bound I-125-T-3 from MCF-7 nuclear extracts by an ER-specific monoclonal antibody and by the displacement of H-3-estradiol binding to ER by radioinert T-3. Copyright (C) 1996 Elsevier B.V. Ltd.

Humoral and cell-mediated immunity in large non-toxic multinodular goitre

Humoral and cell-mediated immunity was investigated in fourteen patients with non-toxic multinodular goitre and ten healthy controls by in vitro methods. These included determination of sheep erythrocyte and complement rosette-forming cells in the peripheral blood, immunoglobulin levels, titres of thyroglobulin and microsomal antibodies and migration inhibition test using thyroid extract and phytohemagglutinin. When compared with controls the patients showed high IgA levels and positive response to thyroid antigen in the leucocyte migration inhibition test. There was no correlation between the leucocyte migration results and the presence of auto-antibodies. These findings indicate a possible role of cell-mediated immunity in non-toxic multinodular goitre.

Cytogenetic analysis of a multinodular thyroid goiter

Short-term cultures of a collagenase disaggregated multinodular goiter was shown by cytogenetic analysis to have the mosaic karyotype 47,XX,+7/48,XX,+7,+17/49,XX,+7,+10,+17. No cytogenetic data on goiter are available for comparison with the present case.