RESUMO
Exposure to glyphosate-based herbicides (GBH) and consumption of cafeteria (CAF) diet, which are widespread in Western society, seem to be associated with endometrial hyperplasia (EH). Here, we aimed to evaluate the effects of a subchronic low dose of GBH added to the CAF diet on the rat uterus. Female Wistar rats were fed from postnatal day (PND)21 until PND240 with chow (control) or CAF diet. Since PND140, rats also received GBH (2 mg of glyphosate/kg/day) or water through food, yielding four experimental groups: control, CAF, GBH, and CAF+GBH. On PND240, CAF and CAF+GBH animals showed an increased adiposity index. With respect to the control group, no changes in the serum levels of 17ß-estradiol and progesterone were found. However, progesterone levels were higher in the CAF+GBH group than in the CAF and GBH groups. In the uterus, both studied factors alone and in combination induced morphological and molecular changes associated with EH. Furthermore, the addition of GBH provoked an increased thickness of subepithelial stroma in rats fed with the CAF diet. As a consequence of GBH exposure, CAF+GBH rats exhibited an increased density of abnormal gland area, considered preneoplastic lesions, as well as a reduced PTEN and p27 expression, both tumor suppressor molecules that inhibit cell proliferation, with respect to control rats. These results indicate that the addition of GBH exacerbates the CAF effects on uterine lesions and that the PTEN/p27 signaling pathway seems to be involved. Further studies focusing on the interaction between unhealthy diets and environmental chemicals should be encouraged to better understand uterine pathologies.
Assuntos
Glicina , Glifosato , Herbicidas , Ratos Wistar , Útero , Animais , Feminino , Útero/efeitos dos fármacos , Útero/patologia , Útero/metabolismo , Herbicidas/toxicidade , Glicina/análogos & derivados , Ratos , Hiperplasia Endometrial/induzido quimicamente , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/metabolismo , Progesterona/sangue , Dieta , Estradiol/sangue , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genéticaRESUMO
PURPOSE: To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. METHODS: BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. RESULTS: Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. CONCLUSION: There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.
Assuntos
Inibidores da Aromatase/farmacologia , Carcinogênese/efeitos dos fármacos , Hiperplasia Endometrial/tratamento farmacológico , Nitrilas/farmacologia , Triazóis/farmacologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/etiologia , Animais , Antineoplásicos Hormonais/farmacologia , Inibidores da Aromatase/uso terapêutico , Carcinogênese/patologia , Hiperplasia Endometrial/induzido quimicamente , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/etiologia , Endométrio/efeitos dos fármacos , Endométrio/patologia , Estradiol/sangue , Etilnitrosoureia , Feminino , Letrozol , Acetato de Medroxiprogesterona/farmacologia , Camundongos Endogâmicos BALB C , Nitrilas/uso terapêutico , Progesterona/sangue , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Triazóis/uso terapêuticoRESUMO
PURPOSE: To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. METHODS: BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. RESULTS: Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. CONCLUSION: There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.
Assuntos
Animais , Feminino , Triazóis/farmacologia , Inibidores da Aromatase/farmacologia , Hiperplasia Endometrial/tratamento farmacológico , Carcinogênese/efeitos dos fármacos , Nitrilas/farmacologia , Progesterona/sangue , Fatores de Tempo , Triazóis/uso terapêutico , Adenocarcinoma/etiologia , Adenocarcinoma/tratamento farmacológico , Reprodutibilidade dos Testes , Resultado do Tratamento , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/tratamento farmacológico , Acetato de Medroxiprogesterona/farmacologia , Antineoplásicos Hormonais/farmacologia , Inibidores da Aromatase/uso terapêutico , Hiperplasia Endometrial/induzido quimicamente , Hiperplasia Endometrial/patologia , Endométrio/efeitos dos fármacos , Endométrio/patologia , Estradiol/sangue , Etilnitrosoureia , Carcinogênese/patologia , Camundongos Endogâmicos BALB C , Nitrilas/uso terapêuticoRESUMO
Histopathological effects of cAMP analog (8-Chloro-cAMP), tamoxifen, and medroxyprogesterone, alone or combined, upon BALB/c mice uteri are reported. 8-Chloro-cAMP diminished uterine weight, but did not modify its histopathology or estral cycle significantly. Tamoxifen diminished uterine weight showing cystic hyperplasia and an estral cycle arrested at diestrus. Medroxyprogesterone increased uterine weight, caused a swelling of the endometrium and a pseudopregnancy estrus. When combined with 8-Chloro-cAMP, tamoxifen or medroxyprogesterone always had a predominant effect. We concluded that the effects of 8-Chloro-cAMP on mice uteri did not cause significant changes on its histopathology, but diminished its weight.
Assuntos
8-Bromo Monofosfato de Adenosina Cíclica/análogos & derivados , 8-Bromo Monofosfato de Adenosina Cíclica/efeitos adversos , Tamoxifeno/efeitos adversos , Útero/efeitos dos fármacos , Animais , Hiperplasia Endometrial/induzido quimicamente , Endométrio/efeitos dos fármacos , Endométrio/patologia , Estro/efeitos dos fármacos , Feminino , Medroxiprogesterona/efeitos adversos , Camundongos , Camundongos Endogâmicos BALB C , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Pseudogravidez/induzido quimicamente , Útero/patologiaRESUMO
OBJECTIVE: Endometrial hyperplasia, an entity considered a precursor to endometrial carcinoma, frequently develops in women receiving unopposed estrogens. Progestins used concomitantly with estrogens can largely prevent endometrial hyperplasia and carcinoma. However, the ability of progestins to reverse endometrial hyperplasia induced by estrogens is less well recognized. The purpose of this study was to assess the medical reversal rate of endometrial hyperplasia that develops in women receiving unopposed estrogen replacement therapy (ERT). DESIGN: Review of recent literature (1990-2000). RESULTS: Based on four large series, more than 90% of endometrial hyperplasia caused by ERT can be reversed by medical treatment. Discontinuation of estrogen and oral administration of 10 mg/day of medroxyprogesterone acetate continuously for 6 weeks or cyclically for 3 months (2 weeks of each month) are the two regimens most widely used. Other progestins also have been shown to be effective. CONCLUSIONS: Progestins are highly successful in reversing endometrial hyperplasia caused by ERT.