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)

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

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Fipronil (active ingredient of acaricide frontline (R)) acting on the mice thyroid

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

Detection of numerical chromosome anomalies in interphase cells of benign and malignant thyroid lesions using fluorescence in situ hybridization

Benign and malignant thyroid tumors constitute a wide range of neoplasias showing recurrent chromosome abnormalities. In an attempt to characterize specific numerical chromosome abnormalities in thyroid tissues, We present here the findings from a study of archival samples depicted by 10 malignant tumors, 30 benign lesions, and 10 normal thyroid tissues. Fluorescence in situ hybridization was performed on noncultured samples using biotinylated centromere-specific probes for chromosomes 7, 10, and 17. Trisomy or tetrasomy 7 were present in 19 benign and in 7 malignant tumors. Trisomy 10 or 17 were observed in 18 adenomas or goiters and in 9 carcinomas, and monosomy 17 was seen in 2 carcinomas. Our findings suggest that such abnormalities are an in vivo phenomenon and may be important in the neoplastic proliferation of thyroid gland. (C) Elsevier B.V., 2000. All rights reserved.

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.

THE ASSESSMENT OF ZINC STATUS BY THE ZINC TOLERANCE-TEST IN THYROID-DISEASE

Zinc status was evaluated in 12 hyperthyroid and in 7 hypothyroid patients in comparison with 8 euthyroid individuals by the oral zinc tolerance test and by the determination of urinary zinc excretion. Hyperthyroid patients presented a basal serum concentration similar to that of euthyroid individuals but greater urinary zinc excretion, indicating the occurrence of zinc depletion from tissues to the blood stream caused by the catabolism inherent in the hyperthyroid state. Hyperthyroidism also caused lower zinc assimilation by tissues after zinc ingestion. Hypothyroid individuals present lower basal zinc levels in serum than euthyroid and hyperthyroid individuals and urinary zinc excretion similar to that of euthyroid individuals. No changes in the parameters measured were observed after zinc load, suggesting reduced or delayed intestinal absorption and zinc assimilation by tissues. The present data are indicative of zinc deficiency, the lower intestinal zinc absorption probably being one of the contributing factors.

Clinical features and genetic analysis of four Brazilian kindreds with resistance to thyroid hormone

Objective Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of reduced tissue responsiveness to thyroid hormone usually due to mutations located in the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor beta (TR beta). In the present report we describe the clinical and laboratory characteristics and the genetic analysis of patients with this rare disorder from a Brazilian population.Patients Four unrelated Brazilian families with diagnosis of RTH were studied. Age at diagnosis varied from 14 months to 29 years.Results All affected individuals were clinically euthyroid, except for one patient who presented immediately after birth with hyperthyroidism. All individuals had tachycardia and goitre, elevated concentrations of free thyroid hormones and reduced sensitivity to thyroid hormone. Direct sequencing analysis of the TR beta gene revealed four previously reported mutations: c.949G -> A, c.1313G -> A, c.1357C -> A and c.1358dupC in families A, B, C and D, respectively.Conclusion the present report shows that the frequent mutations described in the thyroid hormone receptor worldwide are also present in the Brazilian population, which is characterized by a variable ethnic background.

Absence of cross-reactivity to myeloperoxidase of anti-thyroid microsomal antibodies in patients with autoimmune thyroid diseases

Background: Thyroperoxidase is the major antigen of the thyroid microsomal antibodies (TMA) detected in autoimmune thyroid diseases. Its amino acid sequence has 44% homology with myeloperoxidase (MPO), an enzyme present in the primary granules of neutrophils and one of the major antineutrophil cytoplasmic antibodies (ANCA) antigens. The objective of the present study was to investigate the presence of cross-reactivity to MPO of TMA. Methods: We studied sera from 51 patients with autoimmune thyroid diseases, all of them TMA-positive. The presence of ANCA was investigated by indirect immunofluorescence and by capture enzyme-linked immunosorbent assay. Results: ANCA were positive in 3.9% of the TMA-positive sera and none of them reacted with MPO. In contrast, the ANCA-positive sera revealed antielastase activity. None of the ANCA-positive cases presented clinical signs of vasculitis. However, these 2 patients had been on prolonged treatment with propylthiouracil. Conclusions: We conclude that there is no cross-reactivity to MPO of TMA in patients with autoimmune thyroid diseases, possibly because of difference in the spatial configuration of the immunodominant region. The presence of ANCA in patients with autoimmune thyroid diseases without evidence of vasculitis might result from propylthiouracil-induced polyclonal activation.

Effects of Short-term Hyper- and Hypoprolactinaemia on Hormones of the Pituitary, Gonad and -Thyroid Axis and on Semen Quality in Male Beagles

Effects of a short-term hyper- and hypoprolactinaemia on serum concentrations of LH, testosterone and semen quality in six male Beagles were investigated. Blood samples were collected at 3-day intervals for 12 weeks. The time span was divided into five 3-week periods: pre-treatment, metoclopramide (MCP) treatment (0.2 mg/kg orally three times daily), cabergoline (CAB) treatment (5 mu g/kg orally once daily), post-treatment 1 and post-treatment 2. In the latter, only semen characteristics were evaluated. Semen parameters were analyzed once per week during the whole 15-week investigation time. At the end of each period, the effects of a single intravenous injection of thyrotropin-releasing hormone (TRH; 10 mu g/kg) on the secretion of prolactin (PRL), LH, testosterone, thyroid-stimulating hormone and thyroxine (T4) were investigated. Pre-treatment serum PRL concentration increased under MCP (p < 0.05), followed by a decrease under CAB administration (p < 0.05). Luteinizing hormone and testosterone concentrations were not affected. Except for straight-line sperm velocity, semen quality did not differ between collection periods. A single iv TRH injection induced a significant PRL increase at 20 min in all experimental periods except during CAB treatment. Luteinizing hormone and testosterone did not show clear TRH-related changes. Basic T4 levels were significantly reduced after CAB treatment ( p < 0.05). The results of the present study demonstrate that MCP-induced short-term hyperprolactinaemia in male beagles does not seriously affect the hypothalamo-pituitary axis and semen quality.

Effect of thermal stress on physiological parameters, feed intake and plasma thyroid hormones concentration in Alentejana, Mertolenga, Frisian and Limousine cattle breeds

The aim of the present study was to assess the heat tolerance of animals of two Portuguese (Alentejana and Mertolenga) and two exotic (Frisian and Limousine) cattle breeds, through the monitoring of physiological acclimatization reactions in different thermal situations characterized by alternate periods of thermoneutrality and heat stress simulated in climatic chambers. In the experiment, six heifers of the Alentejana, Frisian and Mertolenga breeds and four heifers of the Limousine breed were used. The increase in chamber temperatures had different consequences on the animals of each breed. When submitted to heat stress, the Frisian animals developed high thermal polypnea (more than 105 breath movements per minute), which did not prevent an increase in the rectal temperature (from 38.7 degrees C to 40.0 degrees C). However, only a slight depression in food intake and in blood thyroid hormone concentrations was observed under thermal stressful conditions. Under the thermal stressful conditions, Limousine animals decreased food intake by 11.4% and blood triiodothyronine (T3) hormone concentration decreased to 76% of the level observed in thermoneutral conditions. Alentejana animals had similar reactions. The Mertolenga cattle exhibited the highest capacity for maintaining homeothermy: under heat stressful conditions, the mean thermal polypnea increased twofold, but mean rectal temperature did not increase. Mean food intake decreased by only 2% and mean T3 blood concentration was lowered to 85,6% of the concentration observed under thermoneutral conditions. These results lead to the conclusion that the Frisian animals had more difficulty in tolerating high temperatures, the Limousine and Alentejana ones had an intermediate difficulty, and the Mertolenga animals were by far the most heat tolerant.