RESUMO
BACKGROUND: Studies have shown that exposure to environmental chemicals known as endocrine disruptors can cause permanent changes in genital organs, such as the prostate. Among these environmental chemicals stands out bisphenol A (BPA). Another factor associated with prostate changes is the consumption of a high-fat diet. Although the relationship between the consumption of a high-fat diet and an increased risk of prostate cancer is well established, the mechanisms that lead to the establishment of this disease are not completely understood, nor the simultaneous action of BPA and high-fat diet. METHODS: Adult gerbils (100 days old) were divided in four groups (n = 6 per group): Control (C): animals that received a control diet and filtered water; Diet (D): animals that received a high-fat diet and filtered water; BPA: animals that received a control diet and BPA - 50 µg kg-1 day-1 in drinking water; BPA + Diet (BPA + D): animals that received a high-fat diet + BPA - 50 µg kg-1 day-1 in drinking water. After the experimental period (6 months), the dorsolateral and ventral prostate lobes were removed, and analyzed by several methods. RESULTS: Histological analysis indicated premalignant and malignant lesions in both prostatic lobes. However, animals of the D, BPA, and BPA + D groups showed a higher incidence and larger number of prostatic lesions; inflammatory foci were also common. Markers to assess prostate lesions, such as increased activation of the DNA repair system (PCNA-positive cells), androgen receptor (AR), and number of basal cells, confirmed the histology. However, serum levels of testosterone did not change under the experimental conditions. CONCLUSIONS: The results indicated that the methodology used was effective in generating metabolic changes, which directly compromised prostatic homeostasis. Diet and BPA appear to modulate the activation of the AR pathway and thereby optimize tumor establishment in the gerbil prostate.
Assuntos
Compostos Benzidrílicos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Fenóis/efeitos adversos , Próstata , Neoplasias da Próstata , Administração Oral , Animais , Compostos Benzidrílicos/administração & dosagem , Carcinogênese/induzido quimicamente , Carcinogênese/metabolismo , Modelos Animais de Doenças , Disruptores Endócrinos , Estrogênios não Esteroides/administração & dosagem , Estrogênios não Esteroides/efeitos adversos , Gerbillinae , Masculino , Fenóis/administração & dosagem , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , TempoRESUMO
Bisphenol A (BPA) is one hormonally active chemical with potential deleterious effects on reproductive organs, including breast and prostate. In contrast, genistein (GEN) is the major phytoestrogen of soy that presents potential protective effects against hormone-dependent cancers, including that of the prostate. Thus, pregnant Sprague-Dawley rats were treated with BPA at 25 or 250 µg/kg/day by gavage from gestational day (GD) 10-21 with or without dietary GEN at 250 mg/kg/chow (â¼5.5 mg/kg/day). Then, male offspring from different litters were euthanized on post-natal day (PND) 21 and 180. At PND21, BPA 25 exposure induced early prostatic changes while dietary GEN attenuated some deleterious actions this xenoestrogen on epithelial cell proliferation levels, androgen receptor expression and prostatic architecture in male offspring. At PND180, a significant increase in incidence of prostatic multifocal inflammation/reactive hyperplasia and atypical hyperplasia were observed in male offspring from dams that received BPA 25. On the other hand, maternal GEN feeding attenuated some the adverse effects of BPA 25 on prostate disease at late-in-life. This way, the present findings point to preventive action of dietary GEN on deleterious effects of gestational BPA exposure in both early and late prostate development in offspring F1.
Assuntos
Suplementos Nutricionais , Estrogênios não Esteroides/antagonistas & inibidores , Genisteína/uso terapêutico , Fenômenos Fisiológicos da Nutrição Materna , Fitoestrógenos/uso terapêutico , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Próstata/efeitos dos fármacos , Animais , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/antagonistas & inibidores , Compostos Benzidrílicos/toxicidade , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estrogênios não Esteroides/administração & dosagem , Estrogênios não Esteroides/toxicidade , Feminino , Masculino , Fenóis/administração & dosagem , Fenóis/antagonistas & inibidores , Fenóis/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Hiperplasia Prostática/prevenção & controle , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/prevenção & controle , Ratos Sprague-Dawley , Receptores Androgênicos/metabolismo , Organismos Livres de Patógenos Específicos , DesmameRESUMO
Introducción: El objeto de este trabajo clínico es estudiar la eficacia de la administración de Dietilestilbestrol (DES) oral en pacientes con cáncer de próstata avanzado y que han presentado refractariedad al tratamiento con análogos LH-RH y además evaluar los efectos colaterales atribuibles a su uso. Material y métodos: Entre Noviembre de 2010 y Mayo de 2012 se ingresaron en forma consecutiva al estudio 15 pacientes con cáncer prostático avanzado, refractarios a manejo con análogos LH-RH. Edad promedio de los pacientes 69,4 años .Rango 57-80. Se registró el tipo de tratamiento realizado, detallando el manejo hormonal previo al que fueron sometidos. Se consideró refractariedad a los análogos, la detección de 2 alzas consecutivas del APE durante la administración de éstos. Se indicó a los pacientes 1mg. de DES al día. La evaluación del tratamiento se hizo cada 30 días con determinación de APE y registro de efectos colaterales. Resultados: De los 15 pacientes, 8 (53,3 por ciento) disminuyeron su APE inicial, 6 de ellos (40 por ciento) lo hicieron en más de un 50 por ciento de su valor y 2 (13,3 por ciento) disminuyeron el APE pero en menos de un 50 por ciento. 7 pacientes (46,6 por ciento) no disminuyeron su valor de APE y fueron considerados como fracasos. Como efectos colaterales del tratamiento tuvimos 13 pacientes (86,6 por ciento) que presentaron hipersensibilidad de los pezones, pero solo 2 requirieron tratamiento sintomático. 4 pacientes (26,6 por ciento) desarrollaron ginecomastia leve a moderada y no tuvimos ninguna complicación cardiovascular en los 15 pacientes estudiados. Conclusión: Consideramos de acuerdo a nuestros resultados que el DES oral es efectivo como tratamiento en los pacientes que han fallado o son refractarios a la deprivación androgénica por análogos LH-RH, con una baja morbilidad, buena aceptación de los pacientes y de muy bajo costo.
Introduction: The object of this clinical trial is to study the effectiveness of the administration of Diethylstilbestrol (DES) oral in patients with advanced cancer of prostate and that has presented resistance to the treatment with analogs LH-RH and in addition to evaluate the collateral effects attributable to its use. Material and methods: Between November of 2010 and May of 2012 15 patients with advanced prostate cancer, refractory to handling with analogs LH-RH entered themselves in consecutive form the study. Age average of the patients 69, 4 years, Rank 57-80. The type of made treatment was registered, detailing previous the hormonal handling which they were put under. Resistance to the analogs, the detection of 2 consecutive rises of the PSA was considered during the administration of this one. 1 mg. was indicated to the patients of DES to the day. The evaluation of the treatment was made every 30 days with determination of PSA and registry of collateral effects. Results: Of the 15 patients, 8 (53,3 percent) diminished their initial PSA, 5 of them (40 percent)did in more of a 50 percent of their value and 2 (13,3 percent) diminished the PSA but in less of a 50 percent. 7 patients (46,6 percent) did not diminished their value of PSA and were considered like failures. As collateral effects of the treatment we had 13 patients (86,6 percent) who presented hypersensitivity of the nipples, but single 2 required symptomatic treatment, 4 patients (26,6 percent) developed ginecomastia weighs moderate and we did not have any cardiovascular complication in the 15 studied patients. Conclusion: We considered according to our results that the oral DES is effective like treatment in the patients who have failed or ar refractory to the androgenic deprivation by analogs LH-RH, with a low morbidity, good acceptance of the patients and very low cost.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Dietilestilbestrol/administração & dosagem , Estrogênios não Esteroides/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Administração Oral , Estudos ProspectivosRESUMO
Zearalenonesolution was given to dams micesubcutaneouslyat a dose of30 mg/kg body weightat the age ofpregnancy 13 to 18 days.Control micewere given only sesameoil. Furthermore, damsmice were allowed todeliver their litter and pups were weanedon 21 days of age. The live birth index andviability of the F-1 offspring were recorded. Determination of fertility of the F-1 offspring were undertaken by mating interlitters. On days 18 of gestation, the F-1 offspring were killed by cervical dislocation. The observation was performed on the number of live or dead fetus, embryo resorption, the number of implantation and the percentage of gestation loss. The result revealed that administration of zearalenone on days 13 to 18 of gestation caused a significant decreasein the number of implantation as the result of mating between control male with treated female and treated male with tretaed female of the F-1 offspring. It could be concluded that in the F-1 offspring, zearalenone interfered the process of ovarian develoment, stimulated the differentation of the uterus, decreased the fertility of the female and the effect of zearalenon was more persistent in the female than in the male...
Se administró una solución subcutánea de zearalenona en una dosis de 30 mg/kg de peso corporal en ratonas preñadas entre 13 a 18 días de gestación. Los ratones control recibieron sólo aceite de sésamo. Además, a las ratonas preñadas se les permitió amamantar a sus crías para ser destetadas a los 21 días de edad. El índice de nacidos vivos y viabilidad de la descendencia F-1 fuer registrado. La determinación de la fertilidad de la descendencia F-1 se llevó a cabo por apareamiento intercrías. El día 18 de gestación, la descendencia F-1 se sacrificó por dislocación cervical. Se observó el número de fetos vivos y muertos, reabsorción del embrión, número de implantaciones y porcentaje de pérdida de gestación. El resultado reveló que la administración de la zearalenona entre los días 13-18 de gestación causó un significativo descenso en el número de implantaciones, como resultado del apareamiento entre machos controles con hembras tratadas y machos tratados con hembras tratadas (F-1 crías). Se puede concluir que en la descendencia F-1, la zearalenona interfiere en el proceso de desarrollo ovárico, estimulado la diferenciación del útero, disminuyendo la fertilidad de la hembra; además el efecto del zearalenon fue más persistente en la hembra que en el macho...
Assuntos
Masculino , Animais , Gravidez , Camundongos , Estrogênios não Esteroides/administração & dosagem , Fertilidade , Zearalenona/administração & dosagem , Ovário , Prenhez , ReproduçãoRESUMO
The hypothalamic-growth hormone (GH)-liver axis represents a new concept in endocrine regulation of drug toxicity. Preponderant sex differences are found in liver gene expression, mostly dependent on the sexually dimorphic pattern of GH secretion which is set during the neonatal period by gonadal steroids. We tested if GH-dependent sexually dimorphic liver enzymes and proteins was perturbed by neonatal Bisphenol A (BPA) treatment in female rats. Female rats were sc injected with BPA (50 or 500 µg/50 µl) or castor oil vehicle from postnatal day 1 to 10. At five months serum prolactin, pituitary GH, and serum and liver insulin growth factor-I (IGF-I) were measured by RIA. Major urinary proteins (MUPs) were determined by electrophoresis. Liver Cyp2c11, Cyp2c12, Adh1, Hnf6, and Prlr mRNA levels were determined by real time PCR. Pituitary GH content and liver IGF-I concentration were increased by neonatal BPA treatment, indicating partial masculinization of the GH axis in treated females. GH-dependent female predominant liver enzyme genes (Cyp2c12 and Adh1) and a transcription factor (Hnf6) were downregulated or defeminized, while there were no changes in a male predominant gene (Cyp2c11) or protein (MUP). Our findings indicate that perinatal exposure to BPA may compromise the sexually dimorphic capacity of the liver to metabolize drugs and steroids.
Assuntos
Disruptores Endócrinos/toxicidade , Estrogênios não Esteroides/toxicidade , Hormônio do Crescimento/metabolismo , Fígado/efeitos dos fármacos , Fenóis/toxicidade , Hipófise/efeitos dos fármacos , Fatores Etários , Envelhecimento/genética , Envelhecimento/metabolismo , Álcool Desidrogenase/genética , Animais , Animais Recém-Nascidos , Hidrocarboneto de Aril Hidroxilases/genética , Compostos Benzidrílicos , Família 2 do Citocromo P450 , Esquema de Medicação , Eletroforese em Gel de Poliacrilamida , Disruptores Endócrinos/administração & dosagem , Estrogênios não Esteroides/administração & dosagem , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Fator 6 Nuclear de Hepatócito/genética , Injeções Subcutâneas , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/metabolismo , Masculino , Fenóis/administração & dosagem , Hipófise/metabolismo , Prolactina/sangue , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Receptores da Prolactina/genética , Caracteres Sexuais , Fatores Sexuais , Esteroide 16-alfa-Hidroxilase/genética , Esteroide Hidroxilases/genéticaRESUMO
Bisphenol A (BPA) is an estrogenic agonist compound that induces changes in diverse reproductive parameters in rats. The aim of the present study was to determine the effects of BPA given in drinking water containing 10mg/L (approximate dose 1.2mg/kg BW/day), administered chronically to rats during pregnancy and lactation, on reproductive tract parameters of the offspring. 79.2% of the female offspring from BPA-treated mothers presented irregular estrous cycles. As compared to the control group, a significant increase in the thickness of the uterine epithelia and stroma was observed in the BPA group. Additionally, 60% of the female offspring from BPA mothers did not undergo abundant uterine epithelial apoptosis during the estrus phase of the cycle while control animals did. In addition, a down regulation of ERα expression was observed in epithelial cells on estrus day. The results indicate that BPA, when administered chronically in water beverages to dams, modifies the reproductive cycle of the offspring during young adulthood.
Assuntos
Estrogênios não Esteroides/toxicidade , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Reprodução/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Compostos Benzidrílicos , Epitélio/anatomia & histologia , Epitélio/química , Epitélio/efeitos dos fármacos , Receptor alfa de Estrogênio/análise , Estrogênios não Esteroides/administração & dosagem , Ciclo Estral/efeitos dos fármacos , Feminino , Lactação , Fenóis/administração & dosagem , Gravidez , Ratos , Ratos Wistar , Reprodução/fisiologia , Útero/anatomia & histologia , Útero/química , Útero/efeitos dos fármacos , ÁguaRESUMO
A simple, rapid, and sensitive LC method to determine coumestrol incorporated in the lipid nanoemulsions was validated. The analyses were performed at room temperature on a reversed-phase C18 column using a mobile phase composed of methanol/water with 0.1% trifluoracetic acid (70:30, v/v) at 0.8 mL min(-1). The detection was carried out on a UV detector at 343 nm. The linearity, in the range of 0.1-6.0 microg/mL, presented a determination coefficient (r2) of 0.999, calculated by the least square method. No interferences of the oil core or the gelling excipients were detected. The R.S.D. values for intra- and inter-day precision experiments were lower than 2%. The recovery ranged from 99.42% to 100.72%. Finally, the proposed method was successfully applied to determine coumestrol incorporated in the proposed topical formulations.
Assuntos
Antioxidantes/análise , Cumestrol/análise , Estrogênios não Esteroides/análise , Administração Tópica , Antioxidantes/administração & dosagem , Calibragem , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Cumestrol/administração & dosagem , Composição de Medicamentos , Emulsões , Estrogênios não Esteroides/administração & dosagem , Indicadores e Reagentes , Lipídeos , Metanol , Nanopartículas , Fenóis/análise , Reprodutibilidade dos Testes , SolventesRESUMO
OBJECTIVES: To compare the effects of daily ingestion of dietary soy supplementation, low-dose hormone therapy (HT) and placebo on psychological, somatic and urogenital symptoms in postmenopausal women. STUDY DESIGN: A double-blind, randomized, controlled trial. Sixty healthy, symptomatic, postmenopausal women of 40-60 years of age were allocated to use dietary soy supplementation (containing 90 mg of isoflavone) or HT (1mg estradiol and 0.5mg norethisterone acetate) or placebo. MAIN OUTCOME MEASURES: the Menopause Rating Scale (MRS) was used to assess menopausal symptoms at baseline and after 16 weeks of treatment. Intention-to-treat analyses were performed using the chi-square test, Fisher's exact test, the Kruskal-Wallis non-parametric test and analysis of variance (ANOVA). RESULTS: No statistically significant differences were found between the groups with respect to baseline clinical and sociodemographic characteristics. The psychological, somatic and urogenital symptoms analyzed in the MRS improved during treatment in all the groups, except for urogenital symptoms in the placebo group in which no significant changes were detected. Comparison between groups revealed a statistically significant improvement in somatic symptoms (hot flashes and muscle pain) in the users of HT (-45.6%) and dietary soy supplementation (-49.8%). Urogenital symptoms (vaginal dryness) improved significantly in HT users (-38.6%) and in users of the dietary soy supplementation (-31.2%). There was no statistically significant difference between the groups with respect to overall MRS score or to scores obtained in the psychological symptoms subscale. CONCLUSION: Dietary soy supplementation may constitute an effective alternative therapy for somatic and urogenital symptoms of the menopause.
Assuntos
Terapia de Reposição de Estrogênios/métodos , Estrogênios não Esteroides/administração & dosagem , Menopausa/efeitos dos fármacos , Proteínas de Soja/administração & dosagem , Sistema Vasomotor/efeitos dos fármacos , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Fogachos/prevenção & controle , Humanos , Isoflavonas/administração & dosagem , Menopausa/fisiologia , Pessoa de Meia-Idade , Dor/prevenção & controle , Valores de Referência , Resultado do Tratamento , Doenças Vaginais/prevenção & controleRESUMO
We evaluated whether exposure to bisphenol A (BPA) disrupts neonatal follicle development in rats. From postnatal day 1 (PND1) to PND7, pups received corn oil (control), diethylstilbestrol (DES20: 20 µg/kg-d, DES0.2: 0.2 µg/kg-d), or BPA (BPA20: 20mg/kg-d, BPA0.05: 0.05 mg/kg-d). We examined follicular dynamics, multioocyte follicles (MOFs) incidence, proliferation and apoptosis rates, expression of steroid receptors (ERα, ERß, PR, AR) and cyclin-dependent kinase inhibitor 1B (p27) in PND8 ovaries. DES20, DES0.2 and BPA20-ovaries showed fewer primordial follicles and increased growing follicles. DES20-ovaries exhibited increased incidence of MOFs. Oocyte survival, AR, PR and apoptosis were not changed. Primordial and recruited follicles from BPA20-ovaries showed higher p27, whereas ERß and proliferation were both increased in recruited follicles. ERα positive primary follicles increased in BPA 20-ovaries. Results show that BPA reduces the primordial follicle pool by stimulating the neonatal initial recruitment, associated with an increased proliferation rate likely mediated by an estrogenic pathway.
Assuntos
Disruptores Endócrinos/toxicidade , Estrogênios não Esteroides/toxicidade , Células Germinativas/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Fenóis/toxicidade , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Compostos Benzidrílicos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Relação Dose-Resposta a Droga , Disruptores Endócrinos/administração & dosagem , Estrogênios não Esteroides/administração & dosagem , Feminino , Células Germinativas/crescimento & desenvolvimento , Células Germinativas/metabolismo , Células Germinativas/patologia , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Fenóis/administração & dosagem , Insuficiência Ovariana Primária/induzido quimicamente , Isoformas de Proteínas/metabolismo , Ratos , Ratos Wistar , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
OBJECTIVE: To evaluate the effects of soy isoflavone supplementation on profile lipid and endogenous hormone levels. METHODS: In this double-blind, placebo-controlled study, 47 postmenopausal women 47-66 y of age received 40 mg of isoflavone (n = 25) or 40 mg of casein placebo (n = 22). Cardiovascular risk factors were assessed by evaluating lipid profile at baseline and after 6 mo of treatment. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone and beta-estradiol were measured. Urinary isoflavone concentrations (genistein and daidzein) were measured as markers of both compliance and absorption using high performance liquid chromatography. Baseline characteristics were compared by the unpaired Student's t-test. Within-group changes were determined by paired Student's t-test and comparison between the isoflavone and casein placebo groups were determined by analysis of variance. RESULTS: Lipid levels (low-density lipoprotein and total cholesterol) similarly decreased in both groups. High-density lipoprotein increased significantly in both groups and cannot thus be attributable to treatment; the reason for such variation is unknown and can be attributed to chance or to bias (even that of a real placebo effect in both groups or perhaps in spontaneous changes in exercise and dietary habits of patients after their inclusion). Furthermore, in both groups very low-density lipoprotein and triacylglycerol levels increased in a non-significant manner. CONCLUSION: The results of the present study do not support any biologically significant estrogenic effects of isoflavone on the parameters assessed. Further research will be necessary to definitively assess the safety and efficacy of isoflavone.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Hipercolesterolemia/prevenção & controle , Isoflavonas/administração & dosagem , Pós-Menopausa/sangue , Idoso , Análise de Variância , Biomarcadores/urina , Brasil , Doenças Cardiovasculares/sangue , Caseínas/administração & dosagem , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais , Método Duplo-Cego , Estrogênios não Esteroides/administração & dosagem , Feminino , Genisteína/urina , Humanos , Hipercolesterolemia/sangue , Isoflavonas/urina , Pessoa de Meia-Idade , Cooperação do Paciente , Pós-Menopausa/efeitos dos fármacosRESUMO
Hyperplasia and squamous metaplasia of the prostatic epithelium are conditions induced by oestrogens. Diethylstilbestrol (DES) has been banned from cattle used for beef production because of the health risks. The potential use of molecular markers for the detection of illegal oestrogen administration was evaluated by taking samples of prostatic tissue from control bullocks, bullocks which had been treated with oestrogens, and bullocks sacrificed 21 and 90 days after a single dose of DES. The expression of the glycoconjugates was examined by lectinhistochemistry and the lectin binding pattern was characterised in epithelium and connective tissue. In the animals sacrificed after 21 days there was an increase in the binding of one lectin (JAC) and there was an increase in the binding of one of the other lectins (DBA) in the animals sacrificed after 90 days. An increase in SWGA lectin staining was observed in the bullocks that had probably been treated with oestrogen and in the animals sacrificed 90 days after the inoculation with DES. There were also differences between the binding of SWGA in the control bullocks and the other groups.
Assuntos
Dietilestilbestrol/farmacologia , Estrogênios não Esteroides/farmacologia , Contaminação de Alimentos , Lectinas/metabolismo , Carne , Próstata/efeitos dos fármacos , Animais , Dietilestilbestrol/administração & dosagem , Dietilestilbestrol/metabolismo , Estrogênios não Esteroides/administração & dosagem , Estrogênios não Esteroides/metabolismo , Injeções Intramusculares , Masculino , Próstata/metabolismo , Ligação ProteicaRESUMO
Recent evidence shows that reexpression and upregulation of angiotensin II (ANG II) type 2 (AT2) receptor in adult tissues occur during pathological conditions such as tissue hyperplasia, inflammation, and remodeling. In particular, expression of functional AT2 receptors in the pituitary and their physiological significance and regulation have not been described. In this study, we demonstrate that chronic in vivo estrogen treatment, which induces pituitary hyperplasia, enhances local AT2 expression (measured by Western blot and RT-PCR) concomitantly with downregulation of ANG II type 1 (AT1) receptors. In vivo progesterone treatment of estrogen-induced pituitary hyperplasia did not modify either the ANG II receptor subtype expression pattern or octapeptide-induced and AT1-mediated calcium signaling. Nevertheless, an unexpected potentiation of the ANG II prolactin-releasing effect was observed in this group, and this response was sensitive to both AT1 and AT2 receptor antagonists. These data are the first to document that ANG II can act at the pituitary level through the AT2 receptor subtype and that estrogens display a differential regulation of AT1 and AT2 receptors at this level.
Assuntos
Doenças da Hipófise/metabolismo , Hipófise/metabolismo , Hipófise/patologia , Prolactina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , 17-alfa-Hidroxiprogesterona/farmacologia , Análise de Variância , Animais , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Dietilestilbestrol/administração & dosagem , Regulação para Baixo , Estrogênios não Esteroides/administração & dosagem , Feminino , Hiperplasia/induzido quimicamente , Doenças da Hipófise/induzido quimicamente , Hipófise/efeitos dos fármacos , Prolactina/efeitos dos fármacos , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/efeitos dos fármacos , Receptor Tipo 2 de Angiotensina/genética , Regulação para CimaRESUMO
Environmental estrogens (xenoestrogens) are chemicals that bind to estrogen receptor, mimic estrogenic actions, and may have adverse effects on both human and wildlife health. Bisphenol A (BPA), a monomer used in the manufacture of epoxy resins and polycarbonate has estrogenic activity. In male rodents prenatal exposure to BPA resulted in modifications at the genital tract level. Our objective was to examine the effects of in utero exposure to low, environmentally relevant levels, of the xenoestrogen BPA on proliferation and differentiation of epithelial and stromal cells on the prepubertal rat ventral prostate. To characterize the periductal stromal cells phenotype the expression of vimentin and smooth muscle alpha-actin was evaluated. Androgen receptor (AR) and prostatic acid phosphatase (PAP) expression were also evaluated in epithelial and stromal compartments. Prenatal exposure to BPA increases the fibroblastic:smooth muscle cells ratio and decreases the number of AR-positive cells of periductal stroma of the ventral prostate. In contrast, no differences in AR expression were observed in epithelial cells between control and BPA-treated groups. No changes in proliferation patterns were observed in epithelial and stromal compartments; however, the expression of PAP was diminished in prostate ductal secretory cells of rats in utero exposed to BPA. Our results suggest that prenatal exposure to BPA altered the differentiation pattern of periductal stromal cells of the ventral prostate. These findings are significant in light of the data on human prostate cancers where alterations in the stroma compartment may enhance the invasive and/or malignant potential of the nascent tumor.
Assuntos
Estrogênios não Esteroides/administração & dosagem , Fenóis/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal , Próstata/citologia , Próstata/efeitos dos fármacos , Fosfatase Ácida/análise , Actinas/análise , Animais , Compostos Benzidrílicos , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Epiteliais/química , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Receptor alfa de Estrogênio , Estrogênios não Esteroides/efeitos adversos , Feminino , Masculino , Fenóis/efeitos adversos , Gravidez , Próstata/fisiologia , Ratos , Ratos Wistar , Receptores Androgênicos/análise , Receptores de Estrogênio/análise , Células Estromais/química , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Vimentina/análiseRESUMO
Apoptosis is the biological process by which follicular cells are eliminated in atretic follicles. The aim of the present study was to examine the in vitro effect of a GnRH-a (leuprolide acetate, LA) and its interactions with FSH, dibutyryl cAMP, and growth factors (IGF-I, EGF, and FGF) on follicular apoptosis in early antral ovarian follicles obtained from prepubertal DES- treated rats. Follicles cultured 24 hr in the absence of hormones showed spontaneous onset of apoptotic DNA fragmentation. The presence of FSH suppressed the spontaneous onset of apoptotic DNA fragmentation (75-85%). Quantitative estimation of DNA cleavage from ovarian follicles revealed no significant changes in DNA fragmentation after in vitro LA treatment (1-100 ng/ml). However, coincubation with LA interfered partially with the effects of FSH on apoptosis suppression. This apoptosis suppression was also obtained by treatment with dibutyryl cAMP (80%), and was partially prevented by the presence of LA in the cultures. Follicles were cultured 24 hr with FGF, EGF, or IGF-I, and these factors suppressed DNA fragmentation (70, 60, and 70% respectively), while the presence of LA (100 ng/ml) in the culture medium prevented this effect. In conclusion, we show that the rescue from apoptotic DNA fragmentation produced in early antral follicles by FSH, cAMP, and growth factors, is prevented by coincubation with LA. This GnRH analog would thus interfere in the pathway of FSH, cAMP and/or growth factors by an as yet unknown mechanism.
Assuntos
Apoptose/efeitos dos fármacos , Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Gonadotropina/agonistas , Leuprolida/farmacologia , Folículo Ovariano/efeitos dos fármacos , Animais , Bucladesina/metabolismo , Células Cultivadas , Meios de Cultura Livres de Soro , Fragmentação do DNA , Dietilestilbestrol/administração & dosagem , Dietilestilbestrol/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Estrogênios não Esteroides/administração & dosagem , Estrogênios não Esteroides/farmacologia , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Fatores de Crescimento de Fibroblastos/metabolismo , Atresia Folicular/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Folículo Ovariano/citologia , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/metabolismo , Ratos , Ratos Sprague-Dawley , Maturidade SexualRESUMO
Os fitoestrogênios säo substâncias vegetais näo esteróides, com atividades estrogênicas agonistas e antagonistas. Possuem açäo estrogênica considerada fraca, se comparados aos estrogênios naturais e sintéticos e säo encontrados principalmente na soja e seus derivados. Muitos autores têm avaliado a possibilidade do uso dos fitoestrogênios como opçäo alternativa de terapia de reposiçäo hormonal (TRH), particularmente para os casos de pacientes com contra-indicaçöes para as terapias convencionais. No presente artigo säo revisados aspectos relevantes acerca das propriedades, metabolismo e aplicabilidade dos fitoestrogênios.
Assuntos
Humanos , Feminino , Doenças Cardiovasculares/prevenção & controle , Estrogênios não Esteroides/administração & dosagem , Estrogênios não Esteroides/farmacologia , Estrogênios não Esteroides/metabolismo , Estrogênios não Esteroides/toxicidade , Estrogênios não Esteroides/uso terapêutico , Neoplasias/prevenção & controle , Osteoporose Pós-Menopausa/prevenção & controle , Pós-Menopausa , Terapia de Reposição de Estrogênios , Flavonas , Terapia de Reposição Hormonal , IsoflavonasRESUMO
We analyzed the intake of selected foods that contain phytoestrogens in relation to breast cancer (BC) risk using data from a hospital-based case-control study performed in Mexico City from 1994 to 1995. A total of 198 women with BC, aged 21-79 years, were individually age matched to an identical number of women with no breast disease. By a direct interview, information on socioeconomic characteristics and diet was obtained. A semiquantitative questionnaire was used to estimate the frequency of consumption of 95 foods. The effect of selected foods that contain phytoestrogens on BC risk was estimated using logistic regression models. The adjusted odds ratio for the consumption of more than one slice of onion per day and BC was 0.27 (95% confidence interval = 0.16-0.47), with a statistically significant trend (p < 0.001). This protective effect remained after adjustment for known risk factors of BC. Among premenopausal women, there was also a protective and significant effect due to the intake of lettuce and spinach and nonsignificant protective effects for the consumption of apples and herbal tea. Additional studies aimed at evaluating the potential protective effect of particular phytoestrogens on BC risk are needed.
Assuntos
Neoplasias da Mama/epidemiologia , Dieta , Estrogênios não Esteroides/administração & dosagem , Isoflavonas , Plantas Comestíveis , Adulto , Idoso , Anticarcinógenos/administração & dosagem , Anticarcinógenos/análise , Neoplasias da Mama/prevenção & controle , Estudos de Casos e Controles , Registros de Dieta , Estrogênios não Esteroides/análise , Feminino , Análise de Alimentos , Humanos , Entrevistas como Assunto , Modelos Logísticos , México/epidemiologia , Pessoa de Meia-Idade , Fitoestrógenos , Preparações de Plantas , Plantas Comestíveis/química , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Xenobiotic estrogens in the environment or diet have received much attention as a possible source of certain hormonal disease states in human and wildlife. Therefore, the detection of estrogenic activity of any substance, especially those related to the food industry, is important. The estrogenic activity of p-hydroxybenzoic acid (PHBA), a compound related to a commonly used group of preservatives in food, cosmetic, and pharmaceutical preparations, was evaluated with immature and adult ovariectomized female mice (CD1) using two well-known bioassays. Subcutaneous administrations (s.c.) of different doses of PHBA were compared with estradiol (E2), and their effects on vaginal cornification and uterotrophic activities were evaluated. Different groups of animals were treated s.c. daily for 3 days with vehicle (corn oil, 0.3 ml/100 g), E2 (1 microgram/100 g), and PHBA (0.5, 5, 50, and 500 micrograms/100 g). Four days after treatment, PHBA produced a dose-dependent response on vaginal cornification and uterotrophic activity in both immature and adult ovariectomized mice. The relative uterotrophic potency of PHBA (500 micrograms/100 g) to E2 (1 microgram/100 g) was 0.0011 in immature mice and 0.0018 in ovariectomized animals.