Search

Made available in DSpace on 2019-10-06T15:44:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-05-01. Added 1 bitstream(s) on 2019-10-09T18:34:54Z : No. of bitstreams: 1 S2359-39972019000200142.pdf: 239355 bytes, checksum: bb698bc40f032f4356658ecb11d9c169 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective: To verify the physiological action of triiodothyronine T3 on the expression of transforming growth factor α (TGFA) mRNA in MCF7 cells by inhibition of RNA Polymerase II and the MAPK/ERK pathway. Materials and methods: The cell line was treated with T3 at a physiological dose (10-9M) for 10 minutes, 1 and 4 hour (h) in the presence or absence of the inhibitors, α-amanitin (RNA polymerase II inhibitor) and PD98059 (MAPK/ERK pathway inhibitor). TGFA mRNA expression was analyzed by RT-PCR. For data analysis, we used ANOVA, complemented with the Tukey test and Student t-test, with a minimum significance of 5%. Results: T3 increases the expression of TGFA mRNA in MCF7 cells in 4 h of treatment. Inhibition of RNA polymerase II modulates the effect of T3 treatment on the expression of TGFA in MCF7 cells. Activation of the MAPK/ERK pathway is not required for T3 to affect the expression of TGFA mRNA. Conclusion: Treatment with a physiological concentration of T3 after RNA polymerase II inhibition altered the expression of TGFA. Inhibition of the MAPK/ERK pathway after T3 treatment does not interfere with the TGFA gene expression in a breast adenocarcinoma cell line. Departamento de Medicina Interna Faculdade de Medicina de Botucatu Universidade Estadual Paulista (UNESP) Universidade Estadual Paulista (UNESP) Departamento de Fisiologia e Biofísica Instituto de Ciencias Biomédicas Universidade de São Paulo (USP) Departamento de Medicina Interna Faculdade de Medicina de Botucatu Universidade Estadual Paulista (UNESP) Universidade Estadual Paulista (UNESP) FAPESP: 2013/05629-4 FAPESP: 2014/15209-5 FAPESP: 2015/09686-8

Made available in DSpace on 2019-10-06T16:34:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-08-15 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Triiodothyronine (T3) and estrogen (E2) play important roles in the bone remodeling process and signaling of receptor activator of the nuclear factor-kappa β (RANKL) and osteoprotegerin (OPG) expressed by osteoblasts. However, little is known of the molecular action of these hormones in conditions of hyperthyroidism and associated E2 in human cells. AIMS: This study evaluated the effects of the physiological concentration of E2 (10 nM), alone or in association with physiological (1 nM) and supraphysiological (10 nM) concentrations of T3, on RANKL and OPG gene expression in human osteoblasts. MAIN METHODS: Alkaline phosphatase and osteocalcin assays were performed to verify the presence of mature osteoblasts. After mimicking the experimental hyperthyroidism in osteoblasts untreated or treated with E2, RANKL and OPG gene expression was analyzed by real-time PCR and protein expression by western Blot and ELISA. Alizarin Red staining analyzed the amount of bone matrix after hormonal treatments. KEY FINDINGS: E2 enhanced the gene expression of OPG when associated with 1 nM and 10 nM T3. E2 was able to restore the bone matrix after an initial decrease using 1 nM and 10 nM T3. The protective effect of E2 on the RANKL and OPG signaling pathway was demonstrated. E2 restored the bone matrix induced by experimental hyperthyroidism. SIGNIFICANCE: The data highlight the importance of E2 to maintain OPG expression and osteoblast activity against possible loss of bone mass, especially in conditions where T3 is in excess. Department of Internal Medicine Botucatu Medical School Univ Estadual Paulista - UNESP Laboratory Biochemistry and Biophysics Butantan Institute, 1500, Avenue Vital Brazil Department of Internal Medicine Botucatu Medical School Univ Estadual Paulista - UNESP FAPESP: 2014/16406-9

Made available in DSpace on 2018-12-11T17:02:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-06-01 High expression levels of hypoxia inducing factor 1 alpha are related to mammary carcinogenesis. In previous studies, we demonstrated that expression of transforming growth factor alpha increases upon treatment with triiodothyronine, but this expression does not occur in cellular models that do not express the estrogen receptor, or when cells are co-treated with the anti-estrogen, tamoxifen. The aim of this study was to determine the effect of the hormone triiodothyronine on the expression of the genes HIF1A and TGFA in the breast cancer cell line MCF7. The cell line was subjected to treatment with triiodothyronine at the supraphysiological dose of 10- 8 M for 10 min, 30 min, 1 h, and 4 h in the presence or absence of actinomycin D, the gene expression inhibitor, cycloheximide, the protein synthesis inhibitor, and LY294002, the phosphoinositide 3 kinase inhibitor. HIF1A and TGFA mRNA expression was analyzed by reverse transcription polymerase chain reaction. For data analysis, we used analysis of variance complemented by Tukey test and an adopted minimum of 5% significance. We found that HIF1A and TGFA expression increased in the presence of triiodothyronine at all times studied. HIF1A expression decreased in triiodothyronine-treated cells when gene transcription was also inhibited; however, TGFA expression decreased after 10 and 30 min of treatment even when transcription was not inhibited. We found that activation of PI3K was necessary for triiodothyronine to modulate HIF1A and TGFA expression. Department of Internal Medicine Botucatu Medical School Univ Estadual Paulista - UNESP, Distrito de Rubi�o Jr s/n Department of Pathology Botucatu Medical School Univ Estadual Paulista - UNESP Department of Morphology Bioscience Institute Univ Estadual Paulista - UNESP Department of Internal Medicine Botucatu Medical School Univ Estadual Paulista - UNESP, Distrito de Rubi�o Jr s/n Department of Pathology Botucatu Medical School Univ Estadual Paulista - UNESP Department of Morphology Bioscience Institute Univ Estadual Paulista - UNESP

Obesity patients are more susceptible to develop COVID-19 severe outcome due to the role of angiotensin-converting enzyme 2 (ACE2) in the viral infection. ACE2 is regulated in the human cells by different genes associated with increased (TLR3, HAT1, HDAC2, KDM5B, SIRT1, RAB1A, FURIN and ADAM10) or decreased (TRIB3) virus replication. RNA-seq data revealed 14857 genes expressed in human subcutaneous adipocytes, including genes mentioned above. Irisin treatment increased by 3-fold the levels of TRIB3 transcript and decreased the levels of other genes. The decrease in FURIN and ADAM10 expression enriched diverse biological processes, including extracellular structure organization. Our results indicate a positive effect of irisin on the expression of multiple genes related to viral infection in the adipose tissue; furthermore, translatable for other tissues and organs targeted by the novel coronavirus and present, thus, promising approaches for the treatment of COVID-19 infection as therapeutic strategy to decrease ACE2 regulatory genes., Highlights • Genes associated with increased virus, SARS-CoV-2, replication are diminished, whereas, the gene that decreases virus replication is elevated by irisin in human subcutaneous adipocytes. • TRIB3 is increased by irisin. • Irisin diminished FURIN and ADAM10 in human subcutaneous adipocytes.

Made available in DSpace on 2015-11-03T15:27:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-11-01. Added 1 bitstream(s) on 2015-11-04T10:15:38Z : No. of bitstreams: 1 S0004-27302014000800833.pdf: 270985 bytes, checksum: 17593a871f9249ed70d7043e87455a9f (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Objective: The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of TH receptor alpha (TR proportional to) mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. Materials and methods: It was examined the involvement of PI3K pathway in mediating T3 effects by treating 3T3-L1 adipocytes with physiological (P = 10nM) or supraphysiological (SI = 100 nM) T3 doses during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey's test was used at 5% significance level. Results: T3 increased TR proportional to mRNA expression in P (1.91 +/- 0.13, p < 0.001), SI (2.14 +/- 0.44, p < 0.001) compared to C group (1 +/- 0.08). This increase was completely abrogated by LY294002 in P (0.53 +/- 0.03, p < 0.001) and SI (0.31 +/- 0.03, p < 0.001). To examine whether TRa is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). The presence of CHX completely abrogated levels TRa mRNA in P (1.15 +/- 0.05, p > 0.001) and SI (0.99 +/- 0.15, p > 0.001), induced by T3. Conclusion: These results demonstrate that the activation of the PI3K signaling pathway has a role in T3-mediated indirect TRa gene expression in 3T3-L1 adipocytes. Institute of Health Sciences, Universidade Federal do Mato Grosso (UFMT), Sinop, MT, Brazil Department of Internal Medicine, Botucatu School of Medicine, University of São Paulo State (Unesp), Botucatu, SP, Brazil FAPESP: 2010/16911-4

Made available in DSpace on 2014-12-03T13:10:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-01-01Bitstream added on 2014-12-03T13:23:11Z : No. of bitstreams: 1 WOS000330657200001.pdf: 1661891 bytes, checksum: 9392d9393b4792008534c4842bd77bd7 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) It has been well established that estrogen plays an important role in the progression and treatment of breast cancer. However, the role of triiodothyronine (T-3) remains controversial. We have previously shown its capacity to stimulate the development of positive estrogen receptor breast carcinoma, induce the expression of genes (PR, TGF-alpha) normally stimulated by estradiol (E-2), and suppress genes (TGF-beta) normally inhibited by E-2. Since T-3 regulates growth hormones, metabolism, and differentiation, it is important to verify its action on other genes normally induced by E-2. Therefore, we used DNA microarrays to compare gene expression patterns in MCF-7 breast adenocarcinoma cells treated with E-2 and T-3. Several genes were modulated by both E-2 and T-3 in MCF-7 cells (Student's t-test, P < 0.05). Specifically, we found eight genes that were differentially expressed after treatment with both E-2 and T-3, including amphiregulin, fibulin 1, claudin 6, pericentriolar material 1, premature ovarian failure 1B, factor for adipocyte differentiation-104, sterile alpha motif domain containing 9, and likely ortholog of rat vacuole membrane protein 1 (fold change > 2.0, pFDR < 0.05). We confirmed our microarray results by real-time PCR. Our findings reveal that certain genes in MCF-7 cells can be regulated by both E-2 and T-3. Univ Sao Paulo State UNESP, Botucatu Sch Med, Dept Internal Med, BR-18618000 Botucatu, SP, Brazil Univ Sao Paulo, Sch Med, Dept Radiol, BR-01246903 Sao Paulo, Brazil AC Camargo Hosp, Res Ctr, BR-01509900 Sao Paulo, Brazil Univ Sao Paulo State, Dept Clin Med, BR-18618000 Botucatu, SP, Brazil Univ Sao Paulo State UNESP, Botucatu Sch Med, Dept Internal Med, BR-18618000 Botucatu, SP, Brazil FAPESP: 02/09798-0

Thyroid hormones regulate energy balance and act on adipokines. However, while it is unclear what the effects are of calorie restriction and high doses of triiodothyronine (T 3 ) on adipokines in obesity, thyroid hormones are illicitly administered in isolation or in association with a hypocaloric diet as an obesity treatment. The present study determined the effect of T 3 on serum concentrations and gene expression of the adipokines leptin, resistin, and adiponectin in calorie-restricted obese rats. Male Wistar rats received a hypercaloric diet for 20 weeks followed by calorie restriction for 8 weeks. The animals were then randomly divided into 3 groups: calorie restriction (OR), OR with 5 μg of T 3 /100 g BW (RS1), and OR with 25 μg of T 3 /100 g BW (RS2) for 2 weeks. Blood and adipose tissue samples were collected for biochemical, hormonal, and gene expression analyses. Serum concentrations of leptin (OR: 3.7±0.6, RS1: 3.8±1, RS2 0.2±0.07 ng/dl) and resistin (OR: 2.5±0.6, RS1: 2.5±0.5, RS2 1.6±0.3 ng/dl) were diminished at the higher dose, while serum adiponectin (OR: 31±7, RS1: 24±5, RS2 26±7 ng/dl) levels were lower in the low dose group. Administration of T 3 reduced leptin gene expression (OR: 0.91±0.1, RS1: 0.95±0.1, RS2 0.22±0.1) only at the higher dose, resistin expression (OR: 1.06±0.2, RS1: 1.04±0.1, RS2 0.88±0.2) was not influenced by T 3 treatment, and adiponectin expression (OR: 1.55±0.5, RS1: 0.95±0.15, RS2 0.97±0.13) was diminished independent of the T 3 dose. These results indicate that T 3 , directly or indirectly, inhibits the expression of leptin and adiponectin in calorie restricted obese animals.

Obesity has become a major public health problem, most commonly treated via dietary restriction to promote weight loss. Although leptin and thyroid hormones are involved in the regulation of energy balance, the role of these hormones after the stabilization of weight loss remains unclear. This study was designed to analyze the effect of thyroid hormone on sustained weight loss and leptin gene expression in obese animals after a loss of 5% to 10% of body weight. Thirty-day–old male Wistar rats were separated into 4 groups: control, obese, calorie restriction (CR), and calorie restriction with triiodothyronine administration (CRT). The obese group had increased weight and adiposity, leptin and insulin levels, and leptin gene expression. Dietary restriction in the CR group resulted in decreased body weight and adiposity, diminished leptin, and increased thyroid hormone receptor β expression. The CRT group, submitted to dietary restriction with concomitant administration of a physiologic triiodothyronine dose, had thyroid hormone receptor β expression at levels comparable with those observed in the control group and simultaneously increased leptin expression as compared with that in the CR group, suggesting that thyroid hormone modulates leptin expression under conditions of calorie restriction. Increased leptin expression in the CRT group did not result in increased circulating leptin or a statistically significant reduction in body weight during the treatment period. These data provide impetus for further study, as a longer treatment period may result in increased circulating leptin and, thus, further reduction in body weight during calorie restriction in an obesity model.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:30:42Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:38:01Z : No. of bitstreams: 1 2-s2.0-84884264499.pdf: 942276 bytes, checksum: 17045a1e8ee4d958b7e3d559fc56068d (MD5) Made available in DSpace on 2014-05-27T11:30:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-09-18 The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of leptin mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. We examined the involvement of this pathway in mediating TH effects by treating 3T3-L1 adipocytes with physiological (P=10nM) or supraphysiological (SI=100 nM) T3 dose during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey's test was used at 5% significance. T3 increased leptin mRNA expression in P (2.26 ± 0.36, p< 0.001), SI (1.99 ±0.22, p< 0.01) compared to C group (1± 0.18). This increase was completely abrogated by LY294002 in P (1.31±0.05, p< 0.001) and SI (1.33±0.31, p< 0.05). Western blotting confirmed these results at protein level, indicating the PI3K pathway dependency. To examine whether leptin is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). In P, the presence of CHX maintained the levels mRNA leptin, but was completely abrogated in SI (1.14±0.09, p> 0.001). These results demonstrate that the activation of the PI3K signaling pathway has a role in TH-mediated direct and indirect leptin gene expression in 3T3-L1 adipocytes. © 2013 Oliveira et al. Department of Internal Medicine Botucatu School of Medicine University of São Paulo State (UNESP), Botucatu, São Paulo Department of Physiology Federal University of São Paulo (UNIFESP), São Paulo Department of Internal Medicine Botucatu School of Medicine University of São Paulo State (UNESP), Botucatu, São Paulo

This study aimed evaluate whether estrogen modulates amphiregulin (AREG) gene expression in breast tumor cells. For this, MCF-7 cells were treated for 1 or 4 hours with estrogen (E2 10−7 M) in the ...

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:18Z : No. of bitstreams: 1 2-s2.0-84874511518.pdf: 447094 bytes, checksum: b79744f190efab28202a9a9e0a1d266c (MD5) Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:18Z : No. of bitstreams: 1 2-s2.0-84874511518.pdf: 447094 bytes, checksum: b79744f190efab28202a9a9e0a1d266c (MD5) Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:18Z : No. of bitstreams: 1 2-s2.0-84874511518.pdf: 447094 bytes, checksum: b79744f190efab28202a9a9e0a1d266c (MD5) Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 μg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 μg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress. © 2013 de Sibio et al. Department of Internal Medicine Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Pathology Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Biostatistics Biosciences Institute - University of Sao Paulo State (UNESP), Botucatu, SP Department of Internal Medicine Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Pathology Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Biostatistics Biosciences Institute - University of Sao Paulo State (UNESP), Botucatu, SP

Made available in DSpace on 2016-04-01T18:44:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2013. Added 1 bitstream(s) on 2016-04-01T18:49:52Z : No. of bitstreams: 1 ISSN0004-2730-2013-57-05-368-374.pdf: 218443 bytes, checksum: 5474d376f1638e12ee42afe0365fd7b3 (MD5) Objetivo: Examinar o efeito de diferentes doses de triiodotironina (T3) sobre a expressão gênica dos receptores TRα e TRβ em diferentes tempos. Materiais e métodos: Adipócitos, 3T3-L1, foram incubados com T3 nas doses fisiológica (F, 10nM) e suprafisiológicas (SI, 100nM ou SII, 1000nM) ou veículo (controle, C) durante 0,5, 1, 6 ou 24h. mRNA dos TRs foram detectados utilizando PCR em tempo real. Resultados: Níveis de TRβ aumentaram em F em 0,5h. Após 1h, níveis de TRα aumentaram em F e SI comparado ao C, enquanto TRβ diminuiu no SII comparado com C, F, e SI. Após 6h, ambos os genes foram suprimidos em todas concentrações. Em 24h, níveis de TRα e TRβ retornaram aos do C. Conclusões: Ação do T3 em F iniciou-se em 1h para TRα e 0,5h para TRβ. Esses resultados são importantes para determinar tempo inicial e dose de T3 em que os receptores de HT são ativados em adipócitos. Objective: To examine the effect of different doses of triiodothyronine (T3) on mRNA levels of thyroid hormone receptors, TRα and TRβ, at different times. Materials and methods: 3T3-L1 adipocytes were incubated with T3 (physiological dose: F; supraphysiological doses: SI or SII), or without T3 (control, C) for 0.5, 1, 6, or 24h. TRα and TRβ mRNA was detected using real-time polymerase chain reaction. Results: F increased TRβ mRNA levels at 0.5h. After 1h, TRα levels increased with F and SI and TRβ levels decreased with SII compared with C, F, and SI. After 6h, both genes were suppressed at all concentrations. In 24h, TRα and TRβ levels were similar to those of C group. Conclusions: T3 action with F began at 1h for TRα and at 0.5h for TRβ. These results suggest the importance of knowing the times and doses that activate T3 receptors in adipocytes. Department of Physiology, São Paulo Federal University (Unifesp), São Paulo, SP, Brazil Department of Internal Clinic, Botucatu Medicine School, São Paulo State University (Unesp), Botucatu, SP, Brazil Department of Biostatistics, Biosciences Institute, Unesp, Botucatu, SP, Brazil

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:26:51Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:31:39Z : No. of bitstreams: 1 2-s2.0-84862333929.pdf: 1588872 bytes, checksum: d84eef3b9c43a00d6f4a6b79900182ab (MD5) Made available in DSpace on 2014-05-27T11:26:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-06-21 Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C)fed with commercial chow ad libitumand obese (OB)fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25g triiodothyronine (T3)/100BW (OT). The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity. Copyright © 2012 Renata de Azevedo Melo Luvizotto et al. Department of Internal Medicine Botucatu School of Medicine University of São Paulo State, 18618-000 Botucatu, SP Department of Sports Center of Physical Education and Sports Federal University of Espirito Santo (UFES), 29075-910 Vitória, ES

Objectives: To examine the effects of triiodothyronine (T3), 17β-estradiol (E2), and tamoxifen (TAM) on transforming growth factor (TGF)-α gene expression in primary breast cancer cell cultures and interactions between the different treatments. Methods and results: Patients included in the study (no.=12) had been newly diagnosed with breast cancer. Fresh human breast carcinoma tissue was cut into 0.3-mm slices. These slices were placed in six 35-mm dishes on 2-ml organ culture medium. Dishes received the following treatments: dish 1: ethanol; dish 2: T3; dish 3: T3+TAM; dish 4: TAM; dish 5: E2; dish 6: E2+TAM. TGF-α mRNA content was normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA levels. All tissues included in this study were positive for estrogen receptor (ER) and thyroid hormone receptor expression. Treatment with T3 for 48 h significantly increased TGF-α mRNA levels compared to controls (15-fold), and concomitant treatment with TAM reduced expression to 3.4-fold compared to controls. When only TAM was added to the culture medium, TGF-α mRNA expression increased 5.3-fold, significantly higher than with all other treatment modalities. Conclusion: We demonstrate that TGF-α mRNA expression is more efficiently upregulated by T3 than E2. Concomitant treatment with TAM had a mitigating effect on the T3 effect, while E2 induced TGF-α upregulation. Our findings show some similarities between primary culture and breast cancer cell lines, but also some important differences: a) induction of TGF-α, a mitogenic protein, by TAM; b) a differential effect of TAM that may depend on relative expression of ER α and β; and c) supraphysiological doses of T3 may induce mitogenic signals in breast cancer tissue under conditions of low circulating E2.