The importance of hormone receptor analysis in osteosarcoma cells growth submitted to treatment with estrogen in association with thyroid hormone

Bone tumor incidence in women peaks at age 50-60, coinciding with the menopause. That estrogen (E2) and triiodothyronine (T3) interact in bone metabolism has been well established. However, few data on the action of these hormones are available. Our purpose was to determine the role of E2 and T3 in the expression of bone activity markers, namely alkaline phosphatase (AP) and receptor activator of nuclear factor κB ligand (RANKL). Two osteosarcoma cell lines: MG-63 (which has both estrogen (ER) and thyroid hormone (TR) receptors) and SaOs-29 (ER receptors only) were treated with infraphysiological E2 associated with T3 at infraphysiological, physiological, and supraphysiological concentrations. Real-time RT-PCR was used for expression analysis. Our results show that, in MG-63 cells, infraphysiological E2 associated with supraphysiological T3 increases AP expression and decreases RANKL expression, while infraphysiological E2 associated with either physiological or supraphysiological T3 decreases both AP and RANKL expression. On the other hand, in SaOs-2 cells, the same hormone combinations had no significant effect on the markers' expression. Thus, the analysis of hormone receptors was shown to be crucial for the assessment of tumor potential growth in the face of hormonal changes. Special care should be provided to patients with T3 and E2 hormone receptors that may increase tumor growth. Copyright © 2007 John Wiley & Sons, Ltd.

Analysis of agonist and antagonist effects on thyroid hormone receptor conformation by hydrogen/deuterium exchange

Thyroid hormone receptors (TRs) are ligand-gated transcription factors with critical roles in development and metabolism. Although x-ray structures of TR ligand-binding domains (LBDs) with agonists are available, comparable structures without ligand (apo-TR) or with antagonists are not. It remains important to understand apo-LBD conformation and the way that it rearranges with ligands to develop better TR pharmaceuticals. In this study, we conducted hydrogen/deuterium exchange on TR LBDs with or without agonist (T 3) or antagonist (NH3). Both ligands reduce deuterium incorporation into LBD amide hydrogens, implying tighter overall folding of the domain. As predicted, mass spectroscopic analysis of individual proteolytic peptides after hydrogen/ deuterium exchange reveals that ligand increases the degree of solvent protection of regions close to the buried ligand-binding pocket. However, there is also extensive ligand protection of other regions, including the dimer surface at H10-H11, providing evidence for allosteric communication between the ligand-binding pocket and distant interaction surfaces. Surprisingly, Cterminal activation helix H12, which is known to alter position with ligand, remains relatively protected from solvent in all conditions suggesting that it is packed against the LBD irrespective of the presence or type of ligand. T 3, but not NH3, increases accessibility of the upper part of H3-H5 to solvent, and we propose that TR H12 interacts with this region in apo-TR and that this interaction is blocked by T 3 but not NH3.Wepresent data from site-directed mutagenesis experiments and molecular dynamics simulations that lend support to this structural model of apo-TR and its ligand-dependent conformational changes. (Molecular Endocrinology 25: 15-31, 2011). Copyright © 2011 by The Endocrine Society.

Clinical diagnosis and histological analysis of vocal nodules and polyps

Recent studies emphasize the importance of the clinical-histology correlation in laryngeal pathologies. Objective: To compare the ENT diagnosis with the pathology diagnosis one of 132 surgical specimens, from 119 patients with vocal nodules and polyps. Method: Retrospective study. We investigated the paraffin blocks corresponding to the lesions of the operated patients. We made new histology cross-sections, totaling 396 new slides, divided into three groups: hematoxylin and eosin, Gomori trichrome and PAS. We analyzed the following histological parameters: epithelium, lamina propria, basement membrane, vascular changes. We compared the laryngological and pathological diagnoses, and we did the statistical analysis, checking the predominant histological aspects in each lesion. Results: There was an agreement between the clinical and pathological diagnoses in 123 (93.18%) of 132 lesions analyzed (42.42% nodules and 50.76% polyps). In the histological parameters we found: epithelial changes such as nodules hyperplasia (82.14%) and polyp atrophy (31.34%). Lamina propria: edema in polyps (71.43%), fibrosis in the nodules (57.14%). Basement membrane: thickened nodules (100%), thin/no change in polyps (100%). There was a predominance of vascular changes in the polyps. Conclusion: We found a high correlation between the ENT diagnosis and the pathology report. Histopathologically, the nodules presented with predominantly epithelial changes, lamina propria and basement membrane fibrosis, while the polyps by changes strictly on the lamina propria and vascular aspects.

Clinical Practice: Vocal nodules in dysphonic children

Common among children, vocal symptoms are a cause of concern for parents who seek elucidation of their diagnosis and treatment. Vocal nodules are the major cause of dysphonias in children and are related to vocal abuse. We conducted a literature review considering clinical, physiopathological, epidemiological, and histological aspects of vocal nodules, as well as diagnostic methods, highlighting the main studies addressing this issue. The controversial points of treatments were also discussed.

Perceptual and acoustic parameters of vocal nodules in children

Vocal nodules constitute the major cause of dysphonia during childhood. Auditory-perceptual and acoustic vocal analyses have been used to differentiate vocal nodules from normal voice in children.Purpose: To study the value of auditory-perceptual and acoustic vocal analyses in assessments of children with nodules.Design: Diagnostic test study.Patients and interventions: A comparative study was carried out including 100 children with videolaryngoscopic diagnosis of vocal nodules (nodule group-NG); and 100 children without vocal symptoms and with normal videolaryngoscopic exams (control group-CG). The age range of both groups was between 4 and 11 years. All children underwent auditory-perceptual vocal analyses (GRBASI scale); maximum phonation time and s/z ratio were calculated, and acoustic vocal analysis (MDVP software) were carried out.Results: There was no difference in the values of maximum phonation time and s/z ratio between groups. Auditory-perceptual analysis indicated greater compromising of voice parameters for NG, compared to CG: G (79 versus 24), R (53 versus 3), B (67 versus 23) and S (35 versus 1). The values of acoustic parameters jitter, PPQ shimmer, APQ, NHR and SPI were higher for NG for CG. The parameter f0 did not differ between groups.Conclusion: Compromising of auditory-perceptual (G, R, B and S) and acoustic vocal parameters (jitter, PPQ shimmer, APQ, NHR and SPI) was greater for children with nodules than for those of the control group, which makes them important methods for assessing child dysphonia. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Thyroid Hormone Stimulates the Proliferation of Sertoli Cells and Single Type A Spermatogonia in Adult Zebrafish (Danio rerio) Testis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Low expression of sodium iodide symporter identifies aggressive thyroid tumors

A decreased radioiodine uptake is frequently detected in differentiated thyroid carcinomas (DTC) and is associated with high recurrence rate and reduced survival. We investigated the correlation between NIS mRNA expression levels in the primary tumor and patient outcome using a quantitative real-time RT-PCR method. NIS expression was decreased in 17 DTC (21.04 +/- 39.66 pg Eq) compared to four autoimune thyroid disease (180.51 +/- 92.63 pg Eq) and 14 normal tissues (75.71 +/- 66.98 pg Eq) (p < 0.0001). The 17 thyroid differentiated carcinoma patients were submitted to surgery complemented by radioiodine ablation and had at least 24 months of follow-up, under levothyroxine continued suppressive therapy. According to their outcome, we could characterize a group of papillary carcinoma patients with aggressive carcinomas, whose NIS mRNA levels were markedly lower than a group with non-aggressive carcinomas (0.62 +/- 0.79 versus 54.87 +/- 53.79: p < 0.005). We suggest that the quantification of NIS mRNA relative levels in the primary tumor may predict poor outcome. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Maternal Thyroid and Glucocorticoid Hormone Interactions in Larval Fish Development, and Their Applications in Aquaculture

Thyroid hormones (THs) have long been known to have regulatory roles in the differentiation and maturation of vertebrate embryos, beginning with the knowledge that hormones of maternal origin are essential for human fetal central nervous and respiratory system development. Precise measurements of circulating THs led to insights into their critically important actions throughout vertebrate growth and development, initially with amphibian metamorphosis and including embryogenesis in fishes. Thyroid cues for larval fish differentiation are enhanced by glucocorticoid hormones, which promote deiodinase activity and thereby increase the generation of triiodothyronine (T-3) from the less bioactive thyroxin (T-4). Glucocorticoids also induce the expression of thyroid hormone receptors in some vertebrates. Maternally derived thyroid hormones and cortisol are deposited in fish egg yolk and accelerate larval organ system differentiation until larvae become capable of endogenous endocrine function. Increases in the T-3/T-4 ratio during larval development may reflect the regulatory importance of maternal thyroid hormones. Experimental applications of individual hormones have produced mixed results, but treatments with combinations of thyroid and corticoid hormones consistently promote larval fish development and improve survival rates. The developmental and survival benefits of maternal endocrine provisioning are increased in viviparous fishes, in which maternal/larval chemical contact is prolonged. Treatments with exogenous thyroid and corticoid hormones consistently promote development and reduce mortality rates in larval fishes, with potential hatchery-scale applications in aquaculture.

Do Thyroid Ultrasonographic Features Change According to Age in Euthyroid Dogs?

The thyroid gland was assessed by ultrasound in healthy euthyroid mixed-breed medium size dogs in different age groups. The objective was to verify ultrasonographic imaging patterns in these groups, as well as to identify possible changes in imaging features resulting from ageing. Thirty dogs - 10 young (<1 year), 10 adult and 10 elderly - without clinical signs or history of thyroid gland disease with complete blood count and thyroid function tests within the reference values were evaluated. Each thyroid lobe was examined by ultrasound for shape, size, echogenicity and echotexture. The analysis of echogenicity and echotexture was made by histogram. Thyroid volume was estimated by the equation for ellipsoid (length x width x height) pi/6. The thyroid volume of the young dogs in this study had a tendency to be higher than in adult dogs (P = 0.068) and older dogs (P = 0.120). The height of the thyroid lobe in the longitudinal plane was significantly higher (P = 0.026) in young dogs compared with the other dogs. The echotexture and echogenicity had no significant differences between groups, but the echogenicity was greater in older dogs. The results point out that ultrasound imaging of the thyroid volume is influenced by age in euthyroid dogs.

Collaboration of ultrasonography in the diagnosis of thyroid gland carcinoma in a dog - case report

The sonographic evaluation of thyroid glands in veterinary medicine presents challenges due to the complexity of the anatomical region, professional experience and type of ultrasonography equipment. The technique is considered a versatile diagnostic method that is noninvasive and has a low cost indicated in different clinical situations. Thyroid carcinoma is a malignant tumor that is often invasive and frequently metastatic to regional lymph nodes and lungs. The prognostic indicators for survival after surgery include tumor size, histological type, mobility and presence or absence of metastasis. The objective of the present report is to demonstrate the importance of ultrasound as a complementary method in the evaluation of thyroid carcinoma in dogs. At the Dr. Halim Atique Veterinary Hospital, an eight-year-old male Pit Bull was examined due to a history of firm painless swelling, approximately six inches in diameter, in the ventral cervical region, for about two months. The sonogram showed a nodular area, with defined and regular margins, and heterogeneous hypoechoic parenchyma, with areas of cavitation and swelling of the thyroid. Histopathology of the nodule was consistent with carcinoma. After thyreoidectomy and hormone replacemet, the patient is in good clinical condition.

Short-term effects of triiodothyronine on thyroid hormone receptor alpha by PI3K pathway in adipocytes, 3T3-L1

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

Circulating thyroid hormone levels in young pregnant rats and their fetuses: Effect of malnutrition

In order to evaluate some factors likely to be involved in the maternal and fetal growth impairment due to alimentary protein deficiency, the circulating levels of triiodothyronine (T 3) and thyroxine (T 4) were studied in 4 young (45-day-old) female rat groups: control and malnourished, both nonpregnant and pregnant; similarly schedules groups were studied using adult (100-day-old) rats. Circulating levels of T 4 were higher in nonpregnant, malnourished young rats in their corresponding controls. T 3 levels were higher in young malnourished animals and lower in adult malnourished animals, nonpregnant or pregnant, as compared to controls. Pups from young malnourished mothers showed significantly lower birth weights than those from controls. The present results suggest that there are age differences in thyroid function, as affected by protein-calorie malnutrition in pregnant and non-pregnant rats. On the other hand, the circulating thyroid hormone levels were not importantly affected by the mother dietary protein restriction under our experimental conditions.

Does radioiodine therapy in patients with differentiated thyroid cancer increase the frequency of another malignant neoplasm?

Objectives. To compare the frequency of another primary malignancy in patients with differentiated thyroid carcinoma (DTC) who received radioiodine therapy or not ((131)I). Material and Methods. 168 cases of DTC patients were retrospectively evaluated as to the frequency of another neoplasia by comparing patients with and without it, taking into account clinical, laboratory, and therapeutic parameters. Results. Another primary malignancy occurred in 8.9% of patients. Of these, 53.3% showed the malignancy before (131)I and 46.7% after it. By comparing both groups, the age at the moment of diagnosis of another neoplasia was 46.1 ± 20.2 years for the group before (131)I therapy and of 69.4 ± 11.4 years for the group after it (P = 0.02). Of the 148 patients treated with (131)I, 4.7% developed another malignancy. The latter were older (61 ± 17 years) than those who did not show another cancer type (44.1 ± 14.2 years) (P < 0.05). Conclusion. The frequency of another neoplasia found after (131)I was similar to that found before (131)I.