RESUMO
Polycystic ovary syndrome (PCOS) is associated with hyperandrogenemia and uterine abnormalities. Our aim was to investigate the uterine effects of PCOS that are mediated through the androgen receptor (AR). After weaning, female rats were treated with sesame oil (Control), dehydroepiandrosterone (DHEA), or DHEA + flutamide (FLU, an AR antagonist) for 20 consecutive days. On postnatal day 41, serum, ovarian and uterine tissues were collected. DHEA and DHEA + FLU rats showed increased testosterone levels. DHEA rats showed increased epithelial height, glandular density, subepithelial stroma and myometrial thickness, associated with decreased nuclei density. These rats also showed increased uterine water content, with decreased aquaporin (AQP) 3, 7 and 8 expression in the uterine epithelium and increased AQP8 expression in the myometrium. DHEA rats also showed decreased uterine collagen remodeling, decreased cell proliferation in the subepithelial stroma, and increased apoptosis in the luminal and glandular epithelium and in the myometrium. They also showed an increase in insulin-like growth factor-1 and a decrease in phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. The uterine stroma of DHEA rats showed no changes in progesterone receptor or estrogen receptor alpha (ERα) and increased AR expression. DHEA + FLU rats showed a smaller increase in the myometrial thickness, an increase in the uterine water content without AQP8 induction and a smaller decrease in collagen remodeling. These rats also showed no apoptosis induction and decreased proliferation in the myometrium, decreased ERα in the subepithelial stroma and myometrium and no modifications in AR. Our results demonstrate that the uterine cell turnover and collagen remodeling in DHEA rats are regulated through AR, directly or indirectly associated with ERα expression.
Assuntos
Desidroepiandrosterona/efeitos adversos , Receptor alfa de Estrogênio/metabolismo , Síndrome do Ovário Policístico/metabolismo , Receptores Androgênicos/metabolismo , Útero/patologia , Animais , Animais Recém-Nascidos , Aquaporinas/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Flutamida/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Síndrome do Ovário Policístico/induzido quimicamente , Ratos , Testosterona/sangue , Testosterona/metabolismo , Útero/efeitos dos fármacos , Útero/metabolismoRESUMO
OBJECTIVES: Polycystic ovary syndrome (PCOS) represents 75% of the cases of anovulatory infertility. The aim of this study was to investigate the role of aspirin on dehydroepiandrosterone (DHEA) - induced polycystic ovary syndrome in Wistar rats. METHODS: Twenty eight (28) pre-pubertal female Wistar rats of 21 days old weighing 16 - 21 g were divided into 4 groups (7 rats/group) and treated as follows; group I received distilled water and served as Control; Group II received 6 mg/100 g body weight DHEA in 0.2 ml of oil subcutaneously to induce PCOS. Group III received 7.5 mg/kg of aspirin orally; Group IV received 6 mg/100kg of body weight of DHEA in 0.2ml of oil subcutaneously and 7.5 mg/kg of aspirin orally. After 15 days of administration, the rats were slaughtered by cervical dislocation. Blood samples and ovaries were collected for reproductive hormonal analysis, biochemical and histopathological analysis. The expressions of mRNA androgen receptor (AR) gene in the ovary were determined by real time reverse transcriptase polymerase chain reaction (qPCR). All the data was analyzed using one way ANOVA with the Graph pad prism software version 6. A p<0.05 was considered significant. RESULTS: The results obtained showed that dehydroepiandrosterone treatment caused significant decrease (p<0.05) in total protein, superoxide Dismutase (SOD), glutathione-s- transferase (GST), Ca2+ ATPase, and significant increase (p<0.05) in malondialdehyde, vascular endothelial growth factor, tumor necrosis factor and estrogen as compared to Controls. The group co-administered with DHEA and aspirin showed significant increases in SOD, GST, CAT, GSH, Progesterone, Ca2+ ATPase, Na+ ATPase, H+ ATPase and significant reduction (p<0.05) in malondialdehyde, VEGF, TNF-α and estrogen as compared with the DHEA group. The histopathological analysis showed reductions in cystic fibrosis, atretic ovaries, increased expression of Bcl-2 and E- Cadherin and reduced Bax expression in the group that received Aspirin and DHEA. CONCLUSION: This study clearly demonstrates that Aspirin has ameliorating effects against polycystic ovary syndrome via anti-inflammatory and hormonal modulatory pathways.
Assuntos
Aspirina/farmacologia , Desidroepiandrosterona/efeitos adversos , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Citocinas/análise , Citocinas/metabolismo , Feminino , Ovário/citologia , Ovário/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/análise , Oxirredutases/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Ratos , Ratos WistarRESUMO
The use of Bisphenol S (BPS) was proposed as an alternative to Bisphenol A (BPA), a chemical employed in the production of polycarbonate plastics and epoxy resins. BPA is a xenoestrogen that affects normal physiology in several species. It was reported that BPS may also act as a xenoestrogen with harmful effects in the reproductive system. Here we studied the effects of BPS during the induction of a polycystic ovarian syndrome (PCOS)-like condition in rats. Animals were injected daily with vehicle, DHEA 60â¯mg/kg, BPS 1⯵g/kg and DHEA-BPS, for 20 days. Cell apoptosis, cell proliferation, and EZRIN expression were analyzed by immunohistochemistry. We found an increase in PCNA expression, which correlates with cytoplasmic accumulation of the polarization marker, EZRIN, in the BPS treated groups. Additionally, the administration of BPS in the DHEA treated group augmented the stratification and number of "intraepithelial lumina" in the endometrial surface epithelium.
Assuntos
Proteínas do Citoesqueleto/metabolismo , Desidroepiandrosterona/administração & dosagem , Endométrio/citologia , Fenóis/administração & dosagem , Síndrome do Ovário Policístico/metabolismo , Sulfonas/administração & dosagem , Regulação para Cima , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desidroepiandrosterona/efeitos adversos , Modelos Animais de Doenças , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Tamanho do Órgão/efeitos dos fármacos , Fenóis/efeitos adversos , Síndrome do Ovário Policístico/induzido quimicamente , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Sulfonas/efeitos adversosRESUMO
The ability of the gonadal hormones to influence diverse immunological functions during the course of several infections has been extensively studied in the latest decades. Testosterone has a suppressive effect on immune response of vertebrates and increases susceptibility toward numerous parasitic diseases. Dehydroepiandrosterone is an abundant steroid hormone secreted by the human adrenal cortex and it is considered potent immune-activator. In this paper, it was examined the effects of DHEA and testosterone supplementation in the thymic atrophy in rats infected with Trypanosoma cruzi, by comparing blood parasitism, thymocyte proliferation, TNF-alpha and IL-12 levels. Our data point in the direction that DHEA treatment triggered enhanced thymocyte proliferation as compared to its infected counterparts and reduced production of TNF-alpha during the acute phase of infection. Oppositely, the lowest values for cells proliferation and IL-12 concentrations were reached in testosterone-supplied animals. The combined treatment testosterone and DHEA improves the effectiveness of the host's immune response, reducing blood parasites and the immunosuppressive effects of male androgens besides increasing IL-12 concentrations and decreasing TNF-alpha levels.
Assuntos
Antiprotozoários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Desidroepiandrosterona/uso terapêutico , Testosterona/uso terapêutico , Timo/efeitos dos fármacos , Animais , Antiprotozoários/efeitos adversos , Desidroepiandrosterona/efeitos adversos , Interleucina-12/sangue , Masculino , Parasitemia , Ratos , Ratos Wistar , Testosterona/efeitos adversos , Timo/citologia , Trypanosoma cruzi , Fator de Necrose Tumoral alfa/sangueRESUMO
The physiological importance of and therapeutic interest in dehydroepiandrosterone (DHEA) has been predominantly in relation to its action as an inhibitor of the promotion and progression of several kinds of tumours, including those of breast, prostate, lung, colon, liver and skin tissues. The aim of the present study was to determine the role of DHEA in diethylstilboestrol (DES)-induced pituitary hyperplasia. Female Sprague-Dawley rats were divided into four treatment groups: DES (implanted s.c. with a 20 mg DES pellet), DHEA (two 50 mg DHEA pellets), DHEA/DES (both DHEA and DES pellets), and controls (not implanted). Every week, all rats were weighed and cycled, and jugular blood samples were obtained. After 7 weeks, rats were killed. Hypophyses were removed and weighed, and serum prolactin, GH, IGF-I and leptin levels were assayed by RIA. DHEA cotreatment reduced pituitary enlargement by 39% in DES-treated rats. It also reduced the hyperprolactinaemia (280.4+/-43.6 ng/ml for DHEA/DES vs 823.5+/- 127.1 ng/ml for DES) and partially reversed the loss of body weight induced by DES. DHEA treatment did not modify the effects of DES on serum GH, IGF-I and leptin levels. But DHEA per se also increased pituitary weight and induced hyperprolactinaemia, although to a lesser degree than DES. We conclude that DHEA administration has beneficial effects on oestrogen-induced pituitary hyperplasia and hyperprolactinaemia, but the fact that DHEA per se also induces diverse hormonal effects and a slight pituitary enlargement limits its use as a possible therapeutic drug.
Assuntos
Desidroepiandrosterona/farmacologia , Hipófise/patologia , Animais , Desidroepiandrosterona/efeitos adversos , Dietilestilbestrol , Feminino , Hormônio do Crescimento/sangue , Hiperplasia , Fator de Crescimento Insulin-Like I/análise , Leptina/sangue , Modelos Animais , Tamanho do Órgão/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Prolactina/sangue , Ratos , Ratos Sprague-DawleyRESUMO
La dehidroepiandrosterona (DHEA) y su ester sulfato (DHEA-S) son los esteroides más abundantes producidos por la corteza suprarrenal. A pesar de que sus funciones específicas no han sido claramente establecidas, se sabe que un aumento en los niveles séricos de la DHEA-S puede ir asociado con anovulación o con muerte fetal. El objetivo de este trabajo fue estudiar el efecto de la administración de la DHEA en dosis de 20 mg/Kg de peso (experimentales) o el vehículo (controles) durante los días 5º al 8º (implantación), 9º al 14º (embriogénesis) y 15º al 19º (crecimiento fetal). El día 20º, los úteros se extrajeron, se fijaron, se pesaron y luego, se disecaron los fetos, se pesaron y se estudiaron macroscópicamente. Cuando la DHEA se administró durante los períodos de implatación y embriogénesis no se obtuvieron fetos a términos. Durante la última etapa (días 15º al 19º), la DHEA produjo una disminución significativa (p<0,0001) en el peso fetal (1,84 gr/feto vs 2,11 gr/feto control), sin alteración de su viabilidad. Los resultados demuestran que la administración de la DHEA durante las etapas de implantación y embriogénesis inhibe total y selectivamente el desarrollo del embrión, mientras que, durante la etapa de crecimiento fetal, la DHEA reduce el peso de los fetos sin alterar su anatomía macroscópica externa.
Assuntos
Ratos , Animais , Feminino , Desidroepiandrosterona/efeitos adversos , Desidroepiandrosterona/uso terapêutico , Estruturas Embrionárias/crescimento & desenvolvimento , Ratos , Esteroides/efeitos adversosRESUMO
Se estudió en ratas el efecto de la DHEA sobre la preñez. El esteroide se administró durante los primeros 5 días de la preñez y al decimoquinto día las ratas fueron sacrificadas. Las ratas que recibieron la DHEA en dosis de 5 mg/kg no se inhibió la preñez y en las tratadas con 10 y 20 mg/kg los porcentajes de preñez fueron del 27 por ciento y 0 por ciento , respectivamente. Al 5 día, los niveles séricos de estradiol, progesterona y testosterona, obtenidos en las ratas tratadas con DHEA, fueron más elevados que en las cotroles. El número de blastocistos normales se redujo significativamente. Estos resultados demuestran que la administración de DHEA durante los primeros días de la preñez inhibe la blastogénesis y que este efecto, dosis dependiente, no parece ser debido a una falta de soporte hormonal sino más bien a una acción directa de la DHEA sobre el embrión.