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Fabio Montico - One of the best experts on this subject based on the ideXlab platform.

  • Structural and molecular features of ventral prostate from senile rats (Sprague-Dawley) submitted or not steroid hormone replacement
    2017
    Co-Authors: Fabio Montico
    Abstract:

    Resumo: A reposição androgênica representa uma alternativa para minimizar os efeitos prejudiciais do desequilíbrio hormonal em homens senis, embora seus efeitos sobre o desenvolvimento de doenças prostáticas ainda seja assunto controvertido. Assim, o objetivo deste estudo foi caracterizar aspectos estruturais e moleculares do lobo ventral da próstata de ratos senis frente à reposição de hormônios esteróides, relacionando as alterações decorrentes da terapia hormonal a possíveis condições de lesões prostáticas. Ratos machos (Sprague- Dawley) foram divididos em um grupo Jovem (JOV) (4 meses), que recebeu óleo de amendoim (5 mL/Kg, s.c.), e grupos senis (10 meses), submetidos aos tratamentos: grupo Senil (SEN): óleo de amendoim (5 mL/Kg, s.c.); grupo Testosterona (TEST): cipionato de testosterona (5 mg/Kg, s.c.); grupo Estrógeno (EST): 17?-estradiol (25 ?g/Kg, s.c.); grupo Castrado (CAS): castração cirúrgica; grupo Castrado-Testosterona (CT): castração e após 30 dias tratamento similar ao grupo TEST; grupo Castrado-Estrógeno (CE): castração e após 30 dias tratamento similar ao grupo EST. Após 30 dias de tratamento, foram coletadas amostras de sangue, para dosagens hormonais séricas, e do lobo ventral, para análises em microscopias de luz e eletrônica de transmissão, morfométricas, imunohistoquímicas e Western Blotting. As moléculas investigadas foram: distroglicanas ? e ? (?-DG e ?-DG), receptor do fator de crescimento homólogo à insulina tipo I (IGFR-1), metaloproteinase-9 de matriz (MMP-9), fator de crescimento do endotélio vascular (VEGF) e endostatina. Redução dos níveis séricos de testosterona foi verificada na senescência, com aumento destes após a reposição hormonal no grupo TEST. O estroma do grupo SEN apresentou hipertrofia e células inflamatórias. Após a reposição hormonal na senescência ou frente à castração, verificou-se atrofia no epitélio, células epiteliais com halo citoplasmático claro ao redor do núcleo, microácinos e manutenção do estroma hipertrófico com células inflamatórias. Diminuição dos níveis das DGs foi verificada na senescência, sendo que após a terapia hormonal ocorreu aumento dos níveis protéicos dessas moléculas, especialmente nos grupos que receberam estradiol. Aumento do IGFR-1 e da MMP-9, bem como distribuição diferencial dessas moléculas no compartimento epitelial, foram observados nos grupos submetidos à reposição hormonal e no grupo CAS. O grupo SEN caracterizou acréscimo dos níveis de VEGF, sendo o inverso observado para a endostatina. A terapia hormonal e a castração levaram à elevação dos níveis de VEGF, sobretudo nos grupos EST, CAS e CE. Em oposição, a endostatina demonstrou-se aumentada especialmente nos grupos submetidos à reposição de testosterona. Os presentes resultados sugeriram que o desequilíbrio entre andrógenos e estrógenos verificado na senescência foi acentuado após a terapia hormonal e a castração, potencializando as alterações estruturais associadas a esse período e rompendo o equilíbrio das sinalizações parácrinas prostáticas, com aumento simultâneo de IGFR-1 e MMP-9 e geração de fatores pró e anti-angiogênicos em resposta ao tratamento com estrógenos e andrógenos, respectivamente. Assim, concluiu-se que a terapia hormonal, apesar de seus efeitos positivos sobre as DGs, gerou microambiente prostático reativo, caracterizado por aumento de um fator mitogênico e da remodelação tecidual bem como por desequilíbrio da angiogênese, o que possivelmente comprometeu a função do órgão e o predispôs a desordens glandulares. ;;Abstract: Androgen replacement is an alternative to minimize the harmful effects of hormonal imbalance in elderly men, even though its influence on the development of prostatic diseases is unclear. Thus, the aim herewith was to characterize structural and molecular features of the ventral prostate of senile rats submitted to steroid hormone replacement, relating the alterations resulting from hormonal therapy to possible prostatic lesions. Male rats (Sprague-Dawley) were divided into Young group (YNG) (4 months old rats), which received peanut oil (5 mL/Kg, s.c.), and senile groups (10 months old rats), submitted to the treatments: Senile group (SEN): peanut oil (5 mL/Kg, s.c.); Testosterone group (TEST): Testosterone Cipionate (5 mg/Kg, s.c.); Estrogen group (EST): 17?-estradiol (25 ?g/Kg, s.c.); Castrated group (CAS): surgical castration; Castrated-Testosterone group (CT): castration and after 30 days treatment similar to TEST group; Castrated-Estrogen group (CE): castration and after 30 days treatment similar to EST group. After 30 days treatment, blood samples were collected for hormonal analysis and ventral prostate samples were processed for light and transmission electronic microscopies, morphometric, immunohistochemical and Western Blotting analysis. The investigated molecules were alfa and beta dystroglycans (?DG and ?DG), insulin-like growth factor receptor-1 (IGFR-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and endostatin. Decreased serum Testosterone levels were verified in senescence, with an increase after hormonal replacement in the TEST group. Hypertrophied stroma with inflammatory cells was seen in the SEN group. After hormonal therapy in the senescence or following castration, atrophic and pale cytoplasmatic epithelial cells, microacini and hypertrophied stroma were observed. Decreased DG levels were verified in senescence, but there was an increase of these levels following hormonal therapy, especially in the groups treated with estradiol. Increased IGFR- 1 and MMP-9 protein levels and differential distribution of these molecules were observed in epithelial compartment in those groups which received hormone replacement and in the CAS group. SEN group showed increased VEGF levels in contrast to decreased endostatin levels. Hormonal therapy and castration led to raised VEGF levels, mainly in EST, CAS and CE groups. On the other hand, endostatin was increased especially in those groups submitted to Testosterone replacement. The present results suggested that the imbalance between androgens and estrogens in senescence was enhanced after hormone replacement and castration, intensifying structural changes associated with this period. Also, there was a disruption of prostatic paracrine signaling balance, with simultaneous increase of IGFR-1 and MMP-9 and generation of pro and anti-angiogenic factors in response to treatment with estrogens and androgens, respectively. Thus, it could be concluded that despite its positive effects on DGs levels, hormonal therapy created a reactive prostatic microenvironment, characterized by increase of a mitogenic factor and tissue remodelling as well as prostatic angiogenesis imbalance, which could compromise glandular functions and lead to the emergence of prostatic lesions

  • Angiogenic and tissue remodeling factors in the prostate of elderly rats submitted to hormonal replacement.
    Anatomical record (Hoboken N.J. : 2007), 2013
    Co-Authors: Fabio Montico, Amanda Cia Hetzl, Eduardo Marcelo Cândido, Valéria Helena Alves Cagnon
    Abstract:

    The influence of senescence and hormone replacement on the onset of pathologic processes in the prostate is not yet fully understood. The aim was to identify the immunoreactivity and protein levels of molecules involved in cell proliferation, tissue remodeling and angiogenesis in the ventral prostate of elderly rodents following hormonal replacement. Male Sprague–Dawley rats were separated into one Young group (4-months old), treated with peanut oil (5 mL kg−1, s.c.), and six Senile groups. The senile rats (10-months old) were subdivided into: Senile group (SEN) (5 mL kg−1 peanut oil, s.c.); Testosterone group (TEST) (5 mg kg−1 Testosterone Cipionate, s.c.); Estrogen group (EST) (25 µg kg−1 17β-estradiol, s.c.); castrated group (CAS) (surgical castration); castrated-Testosterone group (CT) (same treatment as CAS and TEST groups); and castrated-estrogen group (CE) (same treatment as CAS and EST groups). After 30 days, samples of the ventral prostate were harvested for analyses of insulin-like growth factor-1 receptor (IGFR-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and endostatin features. IGFR-1 and MMP-9 showed increased protein levels and epithelial immunolabeling both after hormonal replacement and castration. Increased VEGF levels and reduced endostatin were verified in the SEN group. Hormonal therapy and castration led to a higher increase of VEGF, especially in the EST, CAS, and CE groups. Endostatin increased mainly in the TEST and CT groups. Hormonal therapy in senescence generated a reactive microenvironment characterized by the increase of mitogenic and tissue remodeling factors and by the imbalance of angiogenesis, which possibly compromised organ function and predisposed toward glandular disorders. Anat Rec, 296:1758–1767, 2013. © 2013 Wiley Periodicals, Inc.

  • Hormonal therapy in the senescence: Prostatic microenvironment structure and adhesion molecules.
    Micron (Oxford England : 1993), 2011
    Co-Authors: Fabio Montico, Amanda Cia Hetzl, Eduardo Marcelo Cândido, Wagner José Fávaro, Valéria Helena Alves Cagnon
    Abstract:

    Abstract Hormonal replacement has been utilized to minimize the harmful effects of hormonal imbalance in elderly men. The development and progression of prostatic diseases and their relation to hormone therapy is still unclear. Thus, the aim herewith was to characterize the structure and dystroglycan molecule (DGs) reactivities in the ventral prostatic lobe from elderly rats submitted to steroid hormone replacement. Male rats (Sprague–Dawley) were divided into one Young group and six senile groups. The Young group (YNG) (4 months old) received peanut oil (5 mL/kg, s.c.). The senile rats (10 months old) were submitted to the following treatments: Senile group (SEN) (5 mL/kg peanut oil, s.c.); Testosterone group (TEST) (5 mg/kg Testosterone Cipionate, s.c.); Estrogen group (EST) (25 μg/kg 17β-estradiol, s.c.); Castrated group (CAS) (surgical castration); Castrated–Testosterone (CT) (surgical castration and treatment similar to TEST group); and Castrated–Estrogen (CE) (surgical castration and treatment similar to EST group). After 30 days treatment, blood samples were collected for hormonal analysis and ventral prostate samples were processed for light and transmission electron microscopies, morphometrical analysis, immunohistochemistry and Western Blotting. The results showed decreased serum Testosterone levels in the senescence and increased Testosterone and estrogen plasmatic levels after hormone administration in the TEST and EST groups, respectively, highlighting the therapy efficiency. Hypertrophied stroma and inflammatory cells were verified in the SEN group. After hormone replacement in the senescence or following castration, atrophic epithelium, epithelial cells with clear cytoplasmic halo around the nucleus, microacini and maintenance of hypertrophied stroma were seen. Decreased DG levels were verified in the senescence. After hormonal therapy, increased protein levels of these molecules were observed, especially in those groups which received estradiol. Thus, the occurrence of inflammatory cells, stromal hypertrophy and the presence of cells with clear halo around the nucleus after hormonal therapy probably indicated prostatic paracrine signaling imbalance, suggesting a stromal reactive microenvironment favorable to the development of glandular lesions. However, the increase of DG levels characterized positive effect of steroid hormone replacement on the prostate in the senescence. Thus, it could be concluded that despite having positive effects on important molecules involved in the maintenance of epithelial–stromal interaction and glandular cytoarchitecture, such as DGs, hormonal therapy enhanced structural changes associated with senescence, probably due to increased hormonal imbalance between androgens and estrogens in the prostatic tissue.

  • Structural and molecular features of ventral prostate from senile rats (Sprague-Dawley) submitted or not steroid hormone replacement
    Universidade Estadual de Campinas . Instituto de Biologia, 2011
    Co-Authors: Fabio Montico
    Abstract:

    A reposição androgênica representa uma alternativa para minimizar os efeitos prejudiciais do desequilíbrio hormonal em homens senis, embora seus efeitos sobre o desenvolvimento de doenças prostáticas ainda seja assunto controvertido. Assim, o objetivo deste estudo foi caracterizar aspectos estruturais e moleculares do lobo ventral da próstata de ratos senis frente à reposição de hormônios esteróides, relacionando as alterações decorrentes da terapia hormonal a possíveis condições de lesões prostáticas. Ratos machos (Sprague- Dawley) foram divididos em um grupo Jovem (JOV) (4 meses), que recebeu óleo de amendoim (5 mL/Kg, s.c.), e grupos senis (10 meses), submetidos aos tratamentos: grupo Senil (SEN): óleo de amendoim (5 mL/Kg, s.c.); grupo Testosterona (TEST): cipionato de testosterona (5 mg/Kg, s.c.); grupo Estrógeno (EST): 17?-estradiol (25 ?g/Kg, s.c.); grupo Castrado (CAS): castração cirúrgica; grupo Castrado-Testosterona (CT): castração e após 30 dias tratamento similar ao grupo TEST; grupo Castrado-Estrógeno (CE): castração e após 30 dias tratamento similar ao grupo EST. Após 30 dias de tratamento, foram coletadas amostras de sangue, para dosagens hormonais séricas, e do lobo ventral, para análises em microscopias de luz e eletrônica de transmissão, morfométricas, imunohistoquímicas e Western Blotting. As moléculas investigadas foram: distroglicanas ? e ? (?-DG e ?-DG), receptor do fator de crescimento homólogo à insulina tipo I (IGFR-1), metaloproteinase-9 de matriz (MMP-9), fator de crescimento do endotélio vascular (VEGF) e endostatina. Redução dos níveis séricos de testosterona foi verificada na senescência, com aumento destes após a reposição hormonal no grupo TEST. O estroma do grupo SEN apresentou hipertrofia e células inflamatórias. Após a reposição hormonal na senescência ou frente à castração, verificou-se atrofia no epitélio, células epiteliais com halo citoplasmático claro ao redor do núcleo, microácinos e manutenção do estroma hipertrófico com células inflamatórias. Diminuição dos níveis das DGs foi verificada na senescência, sendo que após a terapia hormonal ocorreu aumento dos níveis protéicos dessas moléculas, especialmente nos grupos que receberam estradiol. Aumento do IGFR-1 e da MMP-9, bem como distribuição diferencial dessas moléculas no compartimento epitelial, foram observados nos grupos submetidos à reposição hormonal e no grupo CAS. O grupo SEN caracterizou acréscimo dos níveis de VEGF, sendo o inverso observado para a endostatina. A terapia hormonal e a castração levaram à elevação dos níveis de VEGF, sobretudo nos grupos EST, CAS e CE. Em oposição, a endostatina demonstrou-se aumentada especialmente nos grupos submetidos à reposição de testosterona. Os presentes resultados sugeriram que o desequilíbrio entre andrógenos e estrógenos verificado na senescência foi acentuado após a terapia hormonal e a castração, potencializando as alterações estruturais associadas a esse período e rompendo o equilíbrio das sinalizações parácrinas prostáticas, com aumento simultâneo de IGFR-1 e MMP-9 e geração de fatores pró e anti-angiogênicos em resposta ao tratamento com estrógenos e andrógenos, respectivamente. Assim, concluiu-se que a terapia hormonal, apesar de seus efeitos positivos sobre as DGs, gerou microambiente prostático reativo, caracterizado por aumento de um fator mitogênico e da remodelação tecidual bem como por desequilíbrio da angiogênese, o que possivelmente comprometeu a função do órgão e o predispôs a desordens glandulares.Androgen replacement is an alternative to minimize the harmful effects of hormonal imbalance in elderly men, even though its influence on the development of prostatic diseases is unclear. Thus, the aim herewith was to characterize structural and molecular features of the ventral prostate of senile rats submitted to steroid hormone replacement, relating the alterations resulting from hormonal therapy to possible prostatic lesions. Male rats (Sprague-Dawley) were divided into Young group (YNG) (4 months old rats), which received peanut oil (5 mL/Kg, s.c.), and senile groups (10 months old rats), submitted to the treatments: Senile group (SEN): peanut oil (5 mL/Kg, s.c.); Testosterone group (TEST): Testosterone Cipionate (5 mg/Kg, s.c.); Estrogen group (EST): 17?-estradiol (25 ?g/Kg, s.c.); Castrated group (CAS): surgical castration; Castrated-Testosterone group (CT): castration and after 30 days treatment similar to TEST group; Castrated-Estrogen group (CE): castration and after 30 days treatment similar to EST group. After 30 days treatment, blood samples were collected for hormonal analysis and ventral prostate samples were processed for light and transmission electronic microscopies, morphometric, immunohistochemical and Western Blotting analysis. The investigated molecules were alfa and beta dystroglycans (?DG and ?DG), insulin-like growth factor receptor-1 (IGFR-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and endostatin. Decreased serum Testosterone levels were verified in senescence, with an increase after hormonal replacement in the TEST group. Hypertrophied stroma with inflammatory cells was seen in the SEN group. After hormonal therapy in the senescence or following castration, atrophic and pale cytoplasmatic epithelial cells, microacini and hypertrophied stroma were observed. Decreased DG levels were verified in senescence, but there was an increase of these levels following hormonal therapy, especially in the groups treated with estradiol. Increased IGFR- 1 and MMP-9 protein levels and differential distribution of these molecules were observed in epithelial compartment in those groups which received hormone replacement and in the CAS group. SEN group showed increased VEGF levels in contrast to decreased endostatin levels. Hormonal therapy and castration led to raised VEGF levels, mainly in EST, CAS and CE groups. On the other hand, endostatin was increased especially in those groups submitted to Testosterone replacement. The present results suggested that the imbalance between androgens and estrogens in senescence was enhanced after hormone replacement and castration, intensifying structural changes associated with this period. Also, there was a disruption of prostatic paracrine signaling balance, with simultaneous increase of IGFR-1 and MMP-9 and generation of pro and anti-angiogenic factors in response to treatment with estrogens and androgens, respectively. Thus, it could be concluded that despite its positive effects on DGs levels, hormonal therapy created a reactive prostatic microenvironment, characterized by increase of a mitogenic factor and tissue remodelling as well as prostatic angiogenesis imbalance, which could compromise glandular functions and lead to the emergence of prostatic lesions

Valéria Helena Alves Cagnon - One of the best experts on this subject based on the ideXlab platform.

  • Angiogenic and tissue remodeling factors in the prostate of elderly rats submitted to hormonal replacement.
    Anatomical record (Hoboken N.J. : 2007), 2013
    Co-Authors: Fabio Montico, Amanda Cia Hetzl, Eduardo Marcelo Cândido, Valéria Helena Alves Cagnon
    Abstract:

    The influence of senescence and hormone replacement on the onset of pathologic processes in the prostate is not yet fully understood. The aim was to identify the immunoreactivity and protein levels of molecules involved in cell proliferation, tissue remodeling and angiogenesis in the ventral prostate of elderly rodents following hormonal replacement. Male Sprague–Dawley rats were separated into one Young group (4-months old), treated with peanut oil (5 mL kg−1, s.c.), and six Senile groups. The senile rats (10-months old) were subdivided into: Senile group (SEN) (5 mL kg−1 peanut oil, s.c.); Testosterone group (TEST) (5 mg kg−1 Testosterone Cipionate, s.c.); Estrogen group (EST) (25 µg kg−1 17β-estradiol, s.c.); castrated group (CAS) (surgical castration); castrated-Testosterone group (CT) (same treatment as CAS and TEST groups); and castrated-estrogen group (CE) (same treatment as CAS and EST groups). After 30 days, samples of the ventral prostate were harvested for analyses of insulin-like growth factor-1 receptor (IGFR-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and endostatin features. IGFR-1 and MMP-9 showed increased protein levels and epithelial immunolabeling both after hormonal replacement and castration. Increased VEGF levels and reduced endostatin were verified in the SEN group. Hormonal therapy and castration led to a higher increase of VEGF, especially in the EST, CAS, and CE groups. Endostatin increased mainly in the TEST and CT groups. Hormonal therapy in senescence generated a reactive microenvironment characterized by the increase of mitogenic and tissue remodeling factors and by the imbalance of angiogenesis, which possibly compromised organ function and predisposed toward glandular disorders. Anat Rec, 296:1758–1767, 2013. © 2013 Wiley Periodicals, Inc.

  • Hormonal therapy in the senescence: Prostatic microenvironment structure and adhesion molecules.
    Micron (Oxford England : 1993), 2011
    Co-Authors: Fabio Montico, Amanda Cia Hetzl, Eduardo Marcelo Cândido, Wagner José Fávaro, Valéria Helena Alves Cagnon
    Abstract:

    Abstract Hormonal replacement has been utilized to minimize the harmful effects of hormonal imbalance in elderly men. The development and progression of prostatic diseases and their relation to hormone therapy is still unclear. Thus, the aim herewith was to characterize the structure and dystroglycan molecule (DGs) reactivities in the ventral prostatic lobe from elderly rats submitted to steroid hormone replacement. Male rats (Sprague–Dawley) were divided into one Young group and six senile groups. The Young group (YNG) (4 months old) received peanut oil (5 mL/kg, s.c.). The senile rats (10 months old) were submitted to the following treatments: Senile group (SEN) (5 mL/kg peanut oil, s.c.); Testosterone group (TEST) (5 mg/kg Testosterone Cipionate, s.c.); Estrogen group (EST) (25 μg/kg 17β-estradiol, s.c.); Castrated group (CAS) (surgical castration); Castrated–Testosterone (CT) (surgical castration and treatment similar to TEST group); and Castrated–Estrogen (CE) (surgical castration and treatment similar to EST group). After 30 days treatment, blood samples were collected for hormonal analysis and ventral prostate samples were processed for light and transmission electron microscopies, morphometrical analysis, immunohistochemistry and Western Blotting. The results showed decreased serum Testosterone levels in the senescence and increased Testosterone and estrogen plasmatic levels after hormone administration in the TEST and EST groups, respectively, highlighting the therapy efficiency. Hypertrophied stroma and inflammatory cells were verified in the SEN group. After hormone replacement in the senescence or following castration, atrophic epithelium, epithelial cells with clear cytoplasmic halo around the nucleus, microacini and maintenance of hypertrophied stroma were seen. Decreased DG levels were verified in the senescence. After hormonal therapy, increased protein levels of these molecules were observed, especially in those groups which received estradiol. Thus, the occurrence of inflammatory cells, stromal hypertrophy and the presence of cells with clear halo around the nucleus after hormonal therapy probably indicated prostatic paracrine signaling imbalance, suggesting a stromal reactive microenvironment favorable to the development of glandular lesions. However, the increase of DG levels characterized positive effect of steroid hormone replacement on the prostate in the senescence. Thus, it could be concluded that despite having positive effects on important molecules involved in the maintenance of epithelial–stromal interaction and glandular cytoarchitecture, such as DGs, hormonal therapy enhanced structural changes associated with senescence, probably due to increased hormonal imbalance between androgens and estrogens in the prostatic tissue.

Sergio Marcelino De Oliveira - One of the best experts on this subject based on the ideXlab platform.

  • A prostata ventral do gerbilo frente as diferentes formas de castração e subsequente reposição hormonal pela testosterona
    [s.n.], 2018
    Co-Authors: Sergio Marcelino De Oliveira
    Abstract:

    Orientador: Sebastião Roberto TabogaDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: A próstata é uma glândula exócrina túbulo-alveolar composta, do sistema genital masculino, que secreta parte do líquido seminal. Sua diferenciação dá-se no início do desenvolvimento embrionário e termina na puberdade, sendo que a testosterona (T) tem papel fundamental no seu desenvolvimento e em sua manutenção, após sua conversão pela enzima 5a.-redutase para uma isoforma cerca de 10 vezes mais potente, a dihidrotestosterona (DHT). Uma série de doenças podem acometer a próstata, dentre elas o câncer e a Hiperplasia Benigna Prostática (HBP), e a principal forma de controle dessas doenças é a diminuição dos níveis séricos de T, que pode ser conseguida através da castração cirúrgica (orquiectomia) e da administração de antiandrógenos (castração química). Algumas das drogas mais usadas na castração química são a flutamida e o acetato de ciproterona. A primeira é um antiandrógeno não-esteroidal que compete com a T e com a DHT pelo receptor de andrógeno (RA) nas células da próstata, e a segunda é uma droga esteroidal que além de competir pelo RA inibe a produção de Hormônio Luteinizante (LH) pela hipófise, o que por sua vez inibe a produção de T pelos testículos. O objetivo desse trabalho foi avaliar, morfológica e histoquimicamente o comportamento do tecido prostático regredido após 30 dias de ablação de T, tanto pela orquiectomia quanto pela castração química, ambas seguidas de administração de T exógena e suspensão do tratamento, respectivamente. Para tanto foram usados 40 gerbilos (Meriones unguiculatus, Criscetidae, Gerbilinae) machos adultos, os quais foram divididos em dois grupos experimentais (G.Ex. 01 e G.Ex. 02) e dois grupos controle (G.e. 01 e G.e. 02). G.Ex. 01 foi constituído por 20 animais os quais sOITeramorquiectomia bilateral e após 30 dias receberam doses de cipionato de testosterona (TC) a uma concentração de 25mm/Kg, em intervalos de 48 horas, durante 21 dias, e os animais foram sacrificados após O,7, 14 e 21 dias do inicio do tratamento com Te. G.Ex 02 (20 animais) recebeu doses semanais e alternadas dos antiandrógenos acetato de ciproterona e flutamida (0,3ml/animal/dia numa concentração de 25mgIKg) diluídos em óleo de milho, durante 30 dias, e após a suspensão do tratamento anti-androgênico os animais foram sacrificados após de O,7, 14 e 21 dias. O 8 G.C. 01 foi constituído por 5 animais adultos não castrados e o G.c. 02 por 5 animais adultos castrados que receberam óleo de milho, o veículo de diluição das drogas. Os resultados demonstraram que, tanto a castração cirúrgica quanto a química provocaram uma drástica regressão do peso do complexo prostático após 30 dias quando comparados com o grupo controle. A dosagem hormonal mostrou uma redução na quantidade de T circulante no caso da castração cirúrgica e na castração química e o L.H. apresentou um aumento durante a castração cirúrgica e uma diminuição durante a castração química. Após 30 dias de castração, em ambos os grupos, houve uma drástica diminuição na altura epitelial, que foi mais intensa em G.Ex 02, que, juntamente com a pequena quantidade de retículo endoplasmático rugoso (RER), caracterizou uma pouca atividade secretora dessas células. As células musculares lisas (CML) apresentaram um fenótipo estrelado e irregular, e houve um pregueamento da membrana basal (MB) acompanhada de uma diminuição na quantidade de vesículas secretoras. Após a reposição hormonal, em G.Ex O1 pôde ser notado um aumento na altura epitelial, acompanhado da presença de numerosas e alargadas cisternas de RER. As CML retomaram seu fenótipo característico, mas passaram a apresentar uma enorme quantidade de RER em seu citoplasma, caracterizando uma modulação de seu fenótipo contrátil para um fenótipo secretor. A suspensão do tratamento antiandrogênico em G.Ex 02 promoveu a retomada da altura do epitélio e um aumento na quantidade de RER, e estas células passaram a apresentar uma grande quantidade de vesículas lipídicas em seu citoplasma basal. Como em G.Ex O1 as CML retomaram seu fenótipo característico, e também apresentaram um aumento na quantidade de RER. Assim, estes dados nos permitem assumir que o tecido prostático apresentou uma notável capacidade de involução após supressão androgênica e uma capacidade de reorganização após reposição hormonal, e os eventos decorrentes da orquiectomia e da subseqüente administração de T mostraram mais intensos para o tecido prostáticoAbstract: The prostate is an exocrine gland of the male genital system, which secretes part of seminal liquidolts differentiation initiates in the beginning of the embryonic development and finishes during the puberty. Testosterone (T) plays an essential role in prostate maintenance, after transformation, by 5a-reductase enzyme, to dehidrotestostorone (DHT) an more potent isoform. As Benign Prostatic Hyperplasia (BPH) and cancer may attack prostate gland, the down regulation of T levels by surgical castration (orchiectomy) or by the administration of anti-androgens drugs, such as flutamide and cyproterone acetate (chemical castration) have been the principal therapies to control these disease. The nonsteroidal antiandrogen flutamide acts by competitive inhibition of the androgen receptors (AR) in the prostate cells. The cyproterone acetate is a steroidal drug besides competing for the AR inhibits Luteinizant Hormone (LH) production on the pituitary gland that themselves inhibit T production by testis. The aim of this work was to evaluate morphologically and histochemically the behavior of prostatic tissue regression after 30 days of T ablation by orchiectomy and by chemical castration, both followed by T administration and suspension oftreatment, respectively. Two experimental groups (Ex.G. 01 and Ex.G. 02) of 20 adult gerbil (Meriones unguiculatus) each were employed. ln the Ex.G.Ol the animais underwent bilateral orchiectomy and after 30 days they received Testosterone Cipionate (TC) doses (25mm/Kg) during 21 days every 48 hours. They were sacrificed at O, 7, 14 and 21 days of the TC treatment beginning. Ex.G. 02 received altemates doses of cyproterone acetate and flutamide (0,3mI/animaI/day, at 25mg/Kg) dissolved in com oil, during 30 days weekly. They were sacrificed at O,7, 14 and 21 days after treatment interruption. As control group 5 animaIs not castrated (C.G.Ol) and 5 castrated animaIs (C.G.02) received com oil, the drug dilution vehicIe. Results showed that after 30 days of both surgical and chemical castration a drastic regression in the prostate weight occurred. Hormonal dosages reveled serum T leveI reduction in both surgical and chemical castration, while serum LH leveI increased during surgical castration and decreased during chemical castration. After 30 days of castration in both groups there were10 intense decreases of epithelium height, more intensive in EX.G. 02, and notable small amount of rugous endoplasmatic reticulum (RER), which characterized a low secretory activity of those cells. Some smooth muscle cells (SMC) showed a spinous and irregular phenotype along with infolding basal membrane and decrease of secretory vesicle amount. After hormonal replacement in EX.G. 01 were noted an increase in epithelial height and a greater RER quantity. Those altered SMC recovered its normal pattem and the considerable number of RER observed in the cytoplasm suggests a modulation of these cells ITom contractile to secretory phenotype. In EX.G. 02 the treatment interruption promoted an increase in epithelial height and in the amount ofRER, besides lots oflipid vesicles at basal cytoplasm. Like in EX.G. 01 SMC retook its normal phenotype, but showed an increase of RER amount to. These data leads to conclude that prostatic tissue showed a high capacity of involution after androgenic ablation and a capacity or reorganization after hormonal replacement, but the events promoted by orchiectomy and T administration appear to be more aggressive to the tissueMestradoBiologia CelularMestre em Ciências Biológica

  • Cellular and extracellular behavior in the gerbil (Meriones unguiculatus) ventral prostate following different types of castration and the consequences of Testosterone replacement
    Cell biology international, 2006
    Co-Authors: Sergio Marcelino De Oliveira, Patricia S.l. Vilamaior, Lara S. Corradi, Rejane Maira Góes, Sebastião Roberto Taboga
    Abstract:

    Mongolian gerbils (Meriones unguiculatus) were grouped into two experimental groups: GEx.01 suffered orchiectomy and after 30 days received doses of Testosterone Cipionate (T), while GEx.02 received weekly and alternated doses of the anti-androgens cyproterone acetate and flutamide for 30 days, and the animals were then euthanized. Structural evaluation reveals a more intense reduction in epithelial height in GEx.02. Smooth muscle cells (SMC) presented a star-shaped aspect after 30 days of hormonal ablation and basal membrane was shown to be more intensely grooved in GEx.01. In both groups, after hormonal replacement, recovery in epithelial height could be noted and the SMC presented its phenotypes, but an increase in RER was seen, characterizing a modulation from its contractile to secreting phenotype. In conclusion, the prostate presented involution capacity after androgen ablation and the ability to reorganize after hormonal replacement, but events resulting from orchiectomy and subsequent T replacement were shown to be more aggressive to the prostate.

  • A prostata ventral do gerbilo frente as diferentes formas de castração e subsequente reposição hormonal pela testosterona
    Universidade Estadual de Campinas. Instituto de Biologia, 2005
    Co-Authors: Sergio Marcelino De Oliveira
    Abstract:

    A próstata é uma glândula exócrina túbulo-alveolar composta, do sistema genital masculino, que secreta parte do líquido seminal. Sua diferenciação dá-se no início do desenvolvimento embrionário e termina na puberdade, sendo que a testosterona (T) tem papel fundamental no seu desenvolvimento e em sua manutenção, após sua conversão pela enzima 5a.-redutase para uma isoforma cerca de 10 vezes mais potente, a dihidrotestosterona (DHT). Uma série de doenças podem acometer a próstata, dentre elas o câncer e a Hiperplasia Benigna Prostática (HBP), e a principal forma de controle dessas doenças é a diminuição dos níveis séricos de T, que pode ser conseguida através da castração cirúrgica (orquiectomia) e da administração de antiandrógenos (castração química). Algumas das drogas mais usadas na castração química são a flutamida e o acetato de ciproterona. A primeira é um antiandrógeno não-esteroidal que compete com a T e com a DHT pelo receptor de andrógeno (RA) nas células da próstata, e a segunda é uma droga esteroidal que além de competir pelo RA inibe a produção de Hormônio Luteinizante (LH) pela hipófise, o que por sua vez inibe a produção de T pelos testículos. O objetivo desse trabalho foi avaliar, morfológica e histoquimicamente o comportamento do tecido prostático regredido após 30 dias de ablação de T, tanto pela orquiectomia quanto pela castração química, ambas seguidas de administração de T exógena e suspensão do tratamento, respectivamente. Para tanto foram usados 40 gerbilos (Meriones unguiculatus, Criscetidae, Gerbilinae) machos adultos, os quais foram divididos em dois grupos experimentais (G.Ex. 01 e G.Ex. 02) e dois grupos controle (G.e. 01 e G.e. 02). G.Ex. 01 foi constituído por 20 animais os quais sOITeramorquiectomia bilateral e após 30 dias receberam doses de cipionato de testosterona (TC) a uma concentração de 25mm/Kg, em intervalos de 48 horas, durante 21 dias, e os animais foram sacrificados após O,7, 14 e 21 dias do inicio do tratamento com Te. G.Ex 02 (20 animais) recebeu doses semanais e alternadas dos antiandrógenos acetato de ciproterona e flutamida (0,3ml/animal/dia numa concentração de 25mgIKg) diluídos em óleo de milho, durante 30 dias, e após a suspensão do tratamento anti-androgênico os animais foram sacrificados após de O,7, 14 e 21 dias. O 8 G.C. 01 foi constituído por 5 animais adultos não castrados e o G.c. 02 por 5 animais adultos castrados que receberam óleo de milho, o veículo de diluição das drogas. Os resultados demonstraram que, tanto a castração cirúrgica quanto a química provocaram uma drástica regressão do peso do complexo prostático após 30 dias quando comparados com o grupo controle. A dosagem hormonal mostrou uma redução na quantidade de T circulante no caso da castração cirúrgica e na castração química e o L.H. apresentou um aumento durante a castração cirúrgica e uma diminuição durante a castração química. Após 30 dias de castração, em ambos os grupos, houve uma drástica diminuição na altura epitelial, que foi mais intensa em G.Ex 02, que, juntamente com a pequena quantidade de retículo endoplasmático rugoso (RER), caracterizou uma pouca atividade secretora dessas células. As células musculares lisas (CML) apresentaram um fenótipo estrelado e irregular, e houve um pregueamento da membrana basal (MB) acompanhada de uma diminuição na quantidade de vesículas secretoras. Após a reposição hormonal, em G.Ex O1 pôde ser notado um aumento na altura epitelial, acompanhado da presença de numerosas e alargadas cisternas de RER. As CML retomaram seu fenótipo característico, mas passaram a apresentar uma enorme quantidade de RER em seu citoplasma, caracterizando uma modulação de seu fenótipo contrátil para um fenótipo secretor. A suspensão do tratamento antiandrogênico em G.Ex 02 promoveu a retomada da altura do epitélio e um aumento na quantidade de RER, e estas células passaram a apresentar uma grande quantidade de vesículas lipídicas em seu citoplasma basal. Como em G.Ex O1 as CML retomaram seu fenótipo característico, e também apresentaram um aumento na quantidade de RER. Assim, estes dados nos permitem assumir que o tecido prostático apresentou uma notável capacidade de involução após supressão androgênica e uma capacidade de reorganização após reposição hormonal, e os eventos decorrentes da orquiectomia e da subseqüente administração de T mostraram mais intensos para o tecido prostáticoThe prostate is an exocrine gland of the male genital system, which secretes part of seminal liquidolts differentiation initiates in the beginning of the embryonic development and finishes during the puberty. Testosterone (T) plays an essential role in prostate maintenance, after transformation, by 5a-reductase enzyme, to dehidrotestostorone (DHT) an more potent isoform. As Benign Prostatic Hyperplasia (BPH) and cancer may attack prostate gland, the down regulation of T levels by surgical castration (orchiectomy) or by the administration of anti-androgens drugs, such as flutamide and cyproterone acetate (chemical castration) have been the principal therapies to control these disease. The nonsteroidal antiandrogen flutamide acts by competitive inhibition of the androgen receptors (AR) in the prostate cells. The cyproterone acetate is a steroidal drug besides competing for the AR inhibits Luteinizant Hormone (LH) production on the pituitary gland that themselves inhibit T production by testis. The aim of this work was to evaluate morphologically and histochemically the behavior of prostatic tissue regression after 30 days of T ablation by orchiectomy and by chemical castration, both followed by T administration and suspension oftreatment, respectively. Two experimental groups (Ex.G. 01 and Ex.G. 02) of 20 adult gerbil (Meriones unguiculatus) each were employed. ln the Ex.G.Ol the animais underwent bilateral orchiectomy and after 30 days they received Testosterone Cipionate (TC) doses (25mm/Kg) during 21 days every 48 hours. They were sacrificed at O, 7, 14 and 21 days of the TC treatment beginning. Ex.G. 02 received altemates doses of cyproterone acetate and flutamide (0,3mI/animaI/day, at 25mg/Kg) dissolved in com oil, during 30 days weekly. They were sacrificed at O,7, 14 and 21 days after treatment interruption. As control group 5 animaIs not castrated (C.G.Ol) and 5 castrated animaIs (C.G.02) received com oil, the drug dilution vehicIe. Results showed that after 30 days of both surgical and chemical castration a drastic regression in the prostate weight occurred. Hormonal dosages reveled serum T leveI reduction in both surgical and chemical castration, while serum LH leveI increased during surgical castration and decreased during chemical castration. After 30 days of castration in both groups there were10 intense decreases of epithelium height, more intensive in EX.G. 02, and notable small amount of rugous endoplasmatic reticulum (RER), which characterized a low secretory activity of those cells. Some smooth muscle cells (SMC) showed a spinous and irregular phenotype along with infolding basal membrane and decrease of secretory vesicle amount. After hormonal replacement in EX.G. 01 were noted an increase in epithelial height and a greater RER quantity. Those altered SMC recovered its normal pattem and the considerable number of RER observed in the cytoplasm suggests a modulation of these cells ITom contractile to secretory phenotype. In EX.G. 02 the treatment interruption promoted an increase in epithelial height and in the amount ofRER, besides lots oflipid vesicles at basal cytoplasm. Like in EX.G. 01 SMC retook its normal phenotype, but showed an increase of RER amount to. These data leads to conclude that prostatic tissue showed a high capacity of involution after androgenic ablation and a capacity or reorganization after hormonal replacement, but the events promoted by orchiectomy and T administration appear to be more aggressive to the tissu

Sebastião Roberto Taboga - One of the best experts on this subject based on the ideXlab platform.

  • Cellular and extracellular behavior in the gerbil (Meriones unguiculatus) ventral prostate following different types of castration and the consequences of Testosterone replacement
    Cell biology international, 2006
    Co-Authors: Sergio Marcelino De Oliveira, Patricia S.l. Vilamaior, Lara S. Corradi, Rejane Maira Góes, Sebastião Roberto Taboga
    Abstract:

    Mongolian gerbils (Meriones unguiculatus) were grouped into two experimental groups: GEx.01 suffered orchiectomy and after 30 days received doses of Testosterone Cipionate (T), while GEx.02 received weekly and alternated doses of the anti-androgens cyproterone acetate and flutamide for 30 days, and the animals were then euthanized. Structural evaluation reveals a more intense reduction in epithelial height in GEx.02. Smooth muscle cells (SMC) presented a star-shaped aspect after 30 days of hormonal ablation and basal membrane was shown to be more intensely grooved in GEx.01. In both groups, after hormonal replacement, recovery in epithelial height could be noted and the SMC presented its phenotypes, but an increase in RER was seen, characterizing a modulation from its contractile to secreting phenotype. In conclusion, the prostate presented involution capacity after androgen ablation and the ability to reorganize after hormonal replacement, but events resulting from orchiectomy and subsequent T replacement were shown to be more aggressive to the prostate.

Amanda Cia Hetzl - One of the best experts on this subject based on the ideXlab platform.

  • Angiogenic and Tissue Remodeling Factors in the Prostate of Elderly Rats Submitted to Hormonal Replacement
    EUA, 2015
    Co-Authors: Montico F, Amanda Cia Hetzl, Em Candido, Cagnon Vha
    Abstract:

    Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The influence of senescence and hormone replacement on the onset of pathologic processes in the prostate is not yet fully understood. The aim was to identify the immunoreactivity and protein levels of molecules involved in cell proliferation, tissue remodeling and angiogenesis in the ventral prostate of elderly rodents following hormonal replacement. Male Sprague-Dawley rats were separated into one Young group (4-months old), treated with peanut oil (5 mL kg(-1), s.c.), and six Senile groups. The senile rats (10-months old) were subdivided into: Senile group (SEN) (5 mL kg(-1) peanut oil, s.c.); Testosterone group (TEST) (5 mg kg(-1) Testosterone Cipionate, s.c.); Estrogen group (EST) (25 mu g kg(-1) 17-estradiol, s.c.); castrated group (CAS) (surgical castration); castrated-Testosterone group (CT) (same treatment as CAS and TEST groups); and castrated-estrogen group (CE) (same treatment as CAS and EST groups). After 30 days, samples of the ventral prostate were harvested for analyses of insulin-like growth factor-1 receptor (IGFR-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and endostatin features. IGFR-1 and MMP-9 showed increased protein levels and epithelial immunolabeling both after hormonal replacement and castration. Increased VEGF levels and reduced endostatin were verified in the SEN group. Hormonal therapy and castration led to a higher increase of VEGF, especially in the EST, CAS, and CE groups. Endostatin increased mainly in the TEST and CT groups. Hormonal therapy in senescence generated a reactive microenvironment characterized by the increase of mitogenic and tissue remodeling factors and by the imbalance of angiogenesis, which possibly compromised organ function and predisposed toward glandular disorders. Anat Rec, 296:1758-1767, 2013. (c) 2013 Wiley Periodicals, Inc.2961117581767Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2008/56493-7

  • Angiogenic and tissue remodeling factors in the prostate of elderly rats submitted to hormonal replacement.
    Anatomical record (Hoboken N.J. : 2007), 2013
    Co-Authors: Fabio Montico, Amanda Cia Hetzl, Eduardo Marcelo Cândido, Valéria Helena Alves Cagnon
    Abstract:

    The influence of senescence and hormone replacement on the onset of pathologic processes in the prostate is not yet fully understood. The aim was to identify the immunoreactivity and protein levels of molecules involved in cell proliferation, tissue remodeling and angiogenesis in the ventral prostate of elderly rodents following hormonal replacement. Male Sprague–Dawley rats were separated into one Young group (4-months old), treated with peanut oil (5 mL kg−1, s.c.), and six Senile groups. The senile rats (10-months old) were subdivided into: Senile group (SEN) (5 mL kg−1 peanut oil, s.c.); Testosterone group (TEST) (5 mg kg−1 Testosterone Cipionate, s.c.); Estrogen group (EST) (25 µg kg−1 17β-estradiol, s.c.); castrated group (CAS) (surgical castration); castrated-Testosterone group (CT) (same treatment as CAS and TEST groups); and castrated-estrogen group (CE) (same treatment as CAS and EST groups). After 30 days, samples of the ventral prostate were harvested for analyses of insulin-like growth factor-1 receptor (IGFR-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and endostatin features. IGFR-1 and MMP-9 showed increased protein levels and epithelial immunolabeling both after hormonal replacement and castration. Increased VEGF levels and reduced endostatin were verified in the SEN group. Hormonal therapy and castration led to a higher increase of VEGF, especially in the EST, CAS, and CE groups. Endostatin increased mainly in the TEST and CT groups. Hormonal therapy in senescence generated a reactive microenvironment characterized by the increase of mitogenic and tissue remodeling factors and by the imbalance of angiogenesis, which possibly compromised organ function and predisposed toward glandular disorders. Anat Rec, 296:1758–1767, 2013. © 2013 Wiley Periodicals, Inc.

  • Hormonal therapy in the senescence: Prostatic microenvironment structure and adhesion molecules.
    Micron (Oxford England : 1993), 2011
    Co-Authors: Fabio Montico, Amanda Cia Hetzl, Eduardo Marcelo Cândido, Wagner José Fávaro, Valéria Helena Alves Cagnon
    Abstract:

    Abstract Hormonal replacement has been utilized to minimize the harmful effects of hormonal imbalance in elderly men. The development and progression of prostatic diseases and their relation to hormone therapy is still unclear. Thus, the aim herewith was to characterize the structure and dystroglycan molecule (DGs) reactivities in the ventral prostatic lobe from elderly rats submitted to steroid hormone replacement. Male rats (Sprague–Dawley) were divided into one Young group and six senile groups. The Young group (YNG) (4 months old) received peanut oil (5 mL/kg, s.c.). The senile rats (10 months old) were submitted to the following treatments: Senile group (SEN) (5 mL/kg peanut oil, s.c.); Testosterone group (TEST) (5 mg/kg Testosterone Cipionate, s.c.); Estrogen group (EST) (25 μg/kg 17β-estradiol, s.c.); Castrated group (CAS) (surgical castration); Castrated–Testosterone (CT) (surgical castration and treatment similar to TEST group); and Castrated–Estrogen (CE) (surgical castration and treatment similar to EST group). After 30 days treatment, blood samples were collected for hormonal analysis and ventral prostate samples were processed for light and transmission electron microscopies, morphometrical analysis, immunohistochemistry and Western Blotting. The results showed decreased serum Testosterone levels in the senescence and increased Testosterone and estrogen plasmatic levels after hormone administration in the TEST and EST groups, respectively, highlighting the therapy efficiency. Hypertrophied stroma and inflammatory cells were verified in the SEN group. After hormone replacement in the senescence or following castration, atrophic epithelium, epithelial cells with clear cytoplasmic halo around the nucleus, microacini and maintenance of hypertrophied stroma were seen. Decreased DG levels were verified in the senescence. After hormonal therapy, increased protein levels of these molecules were observed, especially in those groups which received estradiol. Thus, the occurrence of inflammatory cells, stromal hypertrophy and the presence of cells with clear halo around the nucleus after hormonal therapy probably indicated prostatic paracrine signaling imbalance, suggesting a stromal reactive microenvironment favorable to the development of glandular lesions. However, the increase of DG levels characterized positive effect of steroid hormone replacement on the prostate in the senescence. Thus, it could be concluded that despite having positive effects on important molecules involved in the maintenance of epithelial–stromal interaction and glandular cytoarchitecture, such as DGs, hormonal therapy enhanced structural changes associated with senescence, probably due to increased hormonal imbalance between androgens and estrogens in the prostatic tissue.