Navegando por Palavras-chave "Gene regulation"

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    17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells
    (Soc Study Reproduction, 2012-04-01) Royer, Carine [UNIFESP]; Lucas, Thais Fabiana Gameiro [UNIFESP]; Lazari, Maria de Fatima Magalhaes [UNIFESP]; Porto, Catarina Segreti [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The aim of the present study was to investigate the intracellular signaling events downstream of the classical estrogen receptors (ESRs) and G protein-coupled estrogen receptor 1 (GPER) involved in regulation of proliferation and apoptosis of rat Sertoli cells, in which we have previously described ESR1, ESR2, and GPER. ESRs play a role in Sertoli cell proliferation, and GPER, but not ESRs, plays a role modulating gene expression involved with apoptosis. the present study shows that 17beta-estradiol (E2) and the GPER-selective agonist G-1 rapidly activate phosphatidylinositol 3-kinase (PIK3)/serine threonine protein kinase (AKT) and cyclic AMP response element-binding (CREB) phosphorylation. E2 and the ESR1-selective agonist 4,4',4 ''-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol (PPT) increase the expression of cyclin D1 (CCND1), whereas the ESR2-selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and G-1 do not change the expression of this protein, suggesting that ESR1 is the upstream receptor regulating Sertoli cell proliferation. E2- or PPT-ESR1, through activation of epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase 3/1 (MAPK3/1) and PIK3 pathways, induces upregulation of CCND1. KG-501, the compound that disrupts the phospho-CREB/CREB binding protein (CBP) complex, does not change E2-or PPT-ESR1-mediated CCND1 expression, suggesting that phospho-CREB/cyclic AMP response element/CBP is not involved in the expression of this protein. E2- or G-1-GPER, through activation of EGFR/MAPK3/1 and PIK3 pathways, may be involved in the upregulation of antiapoptotic proteins BCL2 and BCL2L2. E2- or G-1-GPER/EGFR/MAPK3/1/phospho-CREB decreases BAX expression. Taken together, these results show a differential effect of E2-GPER on the CREB-mediated transcription of proapoptotic and antiapoptotic genes of the same BCL2 gene family. ESR1 and GPER can mediate the rapid E2 actions in the Sertoli cells, which in turn can modulate nuclear transcriptional events important for Sertoli cell function and maintenance of normal testis development and homeostasis. Our findings are important to clarify the role of estrogen in a critical period of testicular development, and to direct further studies, which may contribute to better understanding of the causes of male infertility.
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    Effects of the antiestrogen fulvestrant (ICI 182,780) on gene expression of the rat efferent ductules
    (Soc Study Reproduction, 2008-09-01) Yasuhara, Fabiana [UNIFESP]; Gomes, Gisele Renata de Oliveira [UNIFESP]; Siu, Erica Rosanna [UNIFESP]; Suenaga, Claudia Igushi [UNIFESP]; Marostica, Elisabeth [UNIFESP]; Porto, Catarina Segreti [UNIFESP]; Lazari, Maria de Fatima Magalhaes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The efferent ductules express the highest amount of estrogen receptors ESR1 (ERalpha) and ESR2 (ERbeta) within the male reproductive tract. Treatment of rats with the antiestrogen fulvestrant (ICI 182,780) causes inhibition of fluid reabsorption in the efferent ductules, leading to seminiferous tubule atrophy and infertility. To provide a more comprehensive knowledge about the molecular targets for estrogen in the rat efferent ductules, we investigated the effects of ICI 182,780 treatment on gene expression using a microarray approach. Treatment with ICI 182,780 increased or reduced at least 2-fold the expression of 263 and 98 genes, respectively. Not surprisingly, several genes that encode ion channels and macromolecule transporters were affected. Interestingly, treatment with ICI 182,780 markedly altered the expression of genes related to extracellular matrix organization. Matrix metalloproteinase 7 (Mmp7), osteopontin (Spp1), and neuronal pentraxin 1 (Nptx1) were among the most altered genes in this category. Upregulation of Mmp7 and Spp1 and downregulation of Nptx1 were validated by Northern blot. Increase in Mmp7 expression was further confirmed by immunohistochemistry and probably accounted for the decrease in collagen content observed in the efferent ductules of ICI 182,780-treated animals. Downregulation of Nptx1 probably contributed to the extracellular matrix changes and decreased amyloid deposition in the efferent ductules of ICI 182,780-treated animals. Identification of new molecular targets for estrogen action may help elucidate the regulatory role of this hormone in the male reproductive tract.
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    Glucocorticoid receptor in the rat epididymis: Expression, cellular distribution and regulation by steroid hormones
    (Elsevier B.V., 2010-08-30) Silva, Erick J. R. [UNIFESP]; Queiroz, Daniel B. C. [UNIFESP]; Honda, Luciana [UNIFESP]; Avellar, Maria Christina W. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Glucocorticoids regulate several physiological functions, including reproduction, in mammals. Curiously, little is known about glucocorticoid-induced effects on the epididymis, an androgen-dependent tissue with vital role on sperm maturation. Here, RT-PCR, Western blot and immunohistochemical studies were performed to evaluate expression, cellular distribution and hormonal regulation of glucocorticoid receptor (GR) along rat epididymis. the rat orthologue of human GR alpha (mRNA and protein) was detected in caput, corpus and cauda epididymis and immunolocalized in the nucleus and cytoplasm of different epididymal cells (epithelial, smooth muscle and interstitial cells) and nerve fibers. Changes in plasma glucocorticoid and androgen levels differentially regulated GR expression in caput and cauda epididymis by homologous and heterologous mechanisms. in vivo treatment with dexamethasone significantly changed the expression of glucocorticoid-responsive genes and induced ligand-dependent GR nuclear translocation in epithelial cells from epididymis, indicating that GR is fully active in this tissue. Heterologous regulation of androgen receptor expression by glucocorticoids was also demonstrated in cauda epididymis. Our results demonstrate that the epididymis is under glucocorticoid regulation, opening new insights into the roles of this hormone in male fertility. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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    In Vivo Treatments with Fulvestrant and Anastrozole Differentially Affect Gene Expression in the Rat Efferent Ductules
    (Soc Study Reproduction, 2011-01-01) Gomes, Gisele Renata de Oliveira [UNIFESP]; Yasuhara, Fabiana [UNIFESP]; Siu, Erica Rosanna [UNIFESP]; Fernandes, Sheilla Alessandra Ferreira [UNIFESP]; Avellar, Maria Christina Werneck [UNIFESP]; Lazari, Maria de Fatima Magalhaes [UNIFESP]; Porto, Catarina Segreti [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Inst Nacl Farmacol & Biol Mol
    Estrogen plays a key role in maintaining the morphology and function of the efferent ductules We previously demonstrated that the antiestrogen fulvestrant markedly affected gene expression in the rat efferent ductules the mechanism of fulvestrant action to modulate gene expression may involve not only the blockade of ESR1 and ESR2 estrogen receptors, but also the activation of ESR1 and ESR2 when the receptors are tethered to AP 1 or SP1 transcription factors, or the activation of the G protein-coupled estrogen receptor 1 We therefore compared the effects of two strategies to interfere with estrogen action in the rat efferent ductules treatment with fulvestrant or with the aromatase inhibitor anastrozole Whereas fulvestrant markedly increased Mmp7 and Spp1, and reduced Npfx1 mRNA levels, no changes were observed with anastrozole Fulvestrant caused changes in epithelial morphology that were not seen with anastrozole Fulvestrant shifted MMP7 immunolocalization in the epithelial cells from the supranuclear to the apical region, this effect was less pronounced with anastrozole in vitro studies of S-35-methiomne incorporation showed that protein release was increased, whereas tissue protein content in the efferent ductules of fulvestrant-treated rats was decreased Although fulvestrant markedly affected gene expression, no changes were observed on AP 1 and SP1 DNA-binding activity the blockade of ESRs seems to be the major reason explaining the differences between both treatments At least some of the effects of fulvestrant appear to result from compensatory mechanisms activated by the dramatic changes caused by ESR1 blockade