130 resultados para Thyroid Hormone Receptors beta


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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Pós-graduação em Medicina Veterinária - FMVZ

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

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Hypothyroidism is a common endocrine disorder in dogs caused by insufficient production and secretion of thyroid hormones. Most affected dogs have primary hypothyroidism that results from lymphocytic thyroiditis, idiopathic thyroid atrophy, or more rarely, neoplastic destruction. Secondary hypothyroidism resulting from inadequate secretion of thyrotropin (thyroid-stimulating hormone –TSH) from the pituitary gland is less commonly recognized. Tertiary hypothyroidism resulting from a deficiency of hypothalamic thyrotropin-releasing hormone (TRH) has not been documented in dogs. The diagnosis of hypothyroidism in dogs is made on the basis of clinical findings, results of routine laboratory and thyroid gland function tests and response to thyroid hormone replacement. Unfortunately, these tests have high sensitivity, but low specificity, for use in the diagnosis of hypothyroidism. Thyroid hormone supplementation is indicated for the treatment of confirmed hypothyroidism and for the diagnoses of the disease through clinical response to trial therapy

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Spermatogonial stem cells (SSCs) either self-renew or differentiate into spermatogonia that further develop into spermatozoa. Self-renewal occurs when residing in a specific micro-environment (niche) while displacement from the niche would tip the signalling balance towards differentiation. Considering the cystic type of spermatogenesis in fish, the SSC candidates are single type A undifferentiated (A(und)) spermatogonia, enveloped by mostly one niche-forming Sertoli cell. When going through a self-renewal cell cycle, the resulting new single type Aund spermatogonium would have to recruit another Sertoli cell to expand the niche space, while a differentiating germ cell cyle would result in a pair of spermatogonia that remain in contact with their cyst-forming Sertoli cells. In zebrafish, thyroid hormone stimulates the proliferation of Sertoli cells and of type Aund spermatogonia, involving Igf3, a new member of the Igf family. In cystic spermatogenesis, type Aund spermatogonia usually do not leave the niche, so that supposedly the signalling in the niche changes when switching from self-renewal to differentiation. and rzAmh inhibited differentiation of type A(und) spermatogonia as well as Fsh-stimulated steroidogenesis. Thus, for Fsh to efficiently stimulate testis functions, Amh bioactivity should be dampened. We also discovered that Fsh increased Sertoli cell Igf3 gene and protein expression; rzIgf3 stimulated spermatogonial proliferation and Fsh-stimulated spermatogenesis was significantly impaired by inhibiting Igf receptor signaling. We propose that in zebrafish, Fsh is the major regulator of testis functions and, supported by other endocrine systems (e.g. thyroid hormone), regulates Leydig cell steroidogenesis as well as Sertoli cell number and growth factor production to promote spermatogenesis.

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

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Background: Prostate cancer is the second most common cancer diagnosed in men; however its etiology remains unknown. Previous studies have shown that environmental adverse factors, such as maternal nutritional status during pregnancy, can influence fetal development and predispose people to diseases in adult life. The feeding of low-protein diets to pregnant rats result in fetal growth disturbance, androgen/estrogen unbalance and changes in the expression and sensibility of hormone receptors in male offspring. These alterations can promote permanent changes in androgen dependent organs, such as in the prostate. In this sense, we hypothesized that the hormonal unbalance that occurs during aging can lead to an increase in the susceptibility to prostatic disorders. Aim: To evaluate our hypothesis, malnourished male rat offspring were submitted to simultaneous estrogen and testosterone exposure in adulthood, to drive lesions in the rat ventral prostate gland (VP). Methods: 17 week-old Wistar rats (n=48) that received in utero normal protein diet (NP group, AIN93G=17% protein) or low protein diet (RP group, AIN93G modified=6% protein) were given implants with 17β-estradiol plus testosterone administration (NPH and RPH groups) for 17 weeks. The animals were killed at the age of 34 weeks and the VP were excised, weighted and processed for histopathological, immunohistochemical (Ki67, AR, p63, e-caderin, laminin, c-myc and GSTP), biochemical and ultrastructural analysis. Results: Both absolute and relative VP weight from NPH animals were about 30% higher than RPH. Serological data showed that estradiol levels were similar in both groups, but testosterone levels were lower in the RPH male offspring. The steroid hormone exposure in adult life promoted prostate lesions in both RPH and NPH offspring associated with reactive stroma. VP from RPH group exhibited heightened susceptibility to prostatic intraepithelial neoplasia (mainly cribriform and signet ring-cell patterns) and increased the incidence and aggressiveness of prostatitis. In this group, a higher proportion of basal cells, increased proliferation index, lower expression ofthe androgen receptor and increased focus of collagenous micronodules closely associated to epithelial neoplasias were also observed. Conclusion:These observations suggest that maternal protein restriction alters adult prostate response to androgen/estrogen handling and increases susceptibility to prostate diseases. Ethical protocol:CEEA,476/2013 IBB-UNESP; Funding Support: 2009/50204-6 and 2013/09649-0.

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The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.

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Substances that mimic endogenous hormones may alter the cell signaling that govern prostate development and predispose it to developing lesions in adult and senile life. Bisphenol A is able to mimic estrogens, and studies have demonstrated that low levels of exposure to this compound have caused alterations during prostate development. The aim of this study was to describe the prostate development in both male and female neonatal gerbils in normal conditions and under exposure to BPA during intrauterine life, and also to analyze whether the effects of intrauterine exposure to BPA remain in adulthood. Morphological, stereological, three-dimensional reconstruction, and immunohistochemical methods were employed. The results demonstrated that in 1-day-old normal gerbils, the female paraurethral glands and the male ventral lobe are morphologically similar, although its tissue components-epithelial buds (EB), periurethral mesenchyme (PeM), paraurethral mesenchyme (PaM) or ventral mesenchymal pad (VMP), and smooth muscle (SM)-have presented different immunolabeling pattern for androgen receptor (AR), and for proliferating cell nuclear antigen (PCNA). Moreover, we observed a differential response of male and female prostate to intrauterine BPA exposure. In 1-day-old males, the intrauterine exposure to BPA caused a decrease of AR-positive cells in the PeM and SM, and a decrease of the proliferative status in the EB. In contrast, no morphological alterations were observed in ventral prostate of adult males. In 1-day-old females, BPA exposure promoted an increase of estrogen receptor alpha (ERα) positive cells in PeM and PaM, a decrease of AR-positive cells in EB and PeM, besides a reduction of cell proliferation in EB. Additionally, the adult female prostate of BPA-exposed animals presented an increase of AR- and PCNA-positive cells. These results suggest that the prostate of female gerbils were more susceptible to the intrauterine BPA effects, since they became more proliferative in adult life. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.