RESUMO
Estrogens generated within endocrine organs and the reproductive system act as ligands for at least three types of estrogen receptors. Estrogen receptors α (ERα) and ß (ERß) belong to the so-called classical family of estrogen receptors, whereas the G protein-coupled receptor GPR30, also known as GPER-1, has been described as a novel estrogen receptor sited in the cell membrane of target cells. Furthermore, these receptors are under stimulation of a family of exogenous estrogens, known as phytoestrogens, which are a diverse group of non-steroidal plant compounds derived from plant food consumed by humans and animals. Because phytoestrogens are omnipresent in our daily diet, they are becoming increasingly important in both human health and disease. Recent evidence indicates that in addition to classical estrogen receptors, phytoestrogens also activate GPER-1 a relevant observation since GPER-1 is involved in several physiopathological disorders and especially in estrogen-dependent diseases such as breast cancer.The first estrogen receptors discovered were the classical ERα and ERß, but from an evolutionary point of view G protein-coupled receptors trace their origins in history to over a billion years ago suggesting that estrogen receptors like GPER-1 may have been the targets of choice for ancient phytoestrogens and/or estrogens.This review provides a comprehensive and systematic literature search on phytoestrogens and its relationship with classical estrogen receptors and GPER-1 including its role in breast cancer, an issue still under discussion.
Assuntos
Anticarcinógenos/administração & dosagem , Neoplasias da Mama/metabolismo , Antagonistas de Estrogênios/administração & dosagem , Glândulas Mamárias Humanas/efeitos dos fármacos , Fitoestrógenos/administração & dosagem , Receptores Acoplados a Proteínas G/agonistas , Animais , Anticarcinógenos/efeitos adversos , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Exposição Dietética/efeitos adversos , Antagonistas de Estrogênios/efeitos adversos , Feminino , Humanos , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/patologia , Fitoestrógenos/efeitos adversos , Fatores de Proteção , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Medição de Risco , Fatores de Risco , Transdução de Sinais/efeitos dos fármacosRESUMO
Flaxseed is considered a functional food with several health benefits. However, because of its high phytoestrogen content, flaxseed influences hormone metabolism and affects the gonadal biomorphology. In this study, computerized histomorphometry was used to evaluate seminiferous and epididymal tubules, considering the different regions of the epididymis (head, body and tail) of rats subjected to a prolonged diet of flaxseed. Young adult male Wistar rats (n=20) were divided into 2 groups during their lactation period: Control Group (CG), fed casein-based meals and Flaxseed Group (FG), fed a 25% flaxseed meal. After 250 days of continuous ingestion, the animals were euthanized and a blood sample was collected. The testicles and epididymis were removed and fixed in buffered formalin solution. The samples were subjected to routine histological paraffin techniques and stained with hematoxilin and eosin. Immunostaining was performed using an antivimentin antibody for Sertoli cell identification. For morphometry, images of the slides were scanned and analyzed using Image J to determine the epithelial height, tubular and luminal diameter and tubular and luminal area. In the hormonal evaluation, FG had a higher serum concentration of estrogen (P=0.001), but no change was observed in the concentration of testosterone. The morphometric assay of seminiferous tubules and epididymal regions revealed no significant differences between the analyzed groups. Similarly, Sertoli cell quantification showed no significant differences in the FG (P=0.98). These results revealed that the continuous and prolonged intake of 25% flaxseed meals from gestation to 250 days of age, even with a significant increase in serum levels of estradiol, does not exert adverse effects on the testicular and epididymal structure or on the cells participating in the spermatogenesis of rats.(AU)
A semente de linhaça é considerada um alimento funcional com vários efeitos benéficos à saúde. Entretanto, devido ao seu elevado teor de fitoestrógenos, esta semente pode influenciar no metabolismo hormonal e interferir na biomorfologia gonadal. Neste estudo, utilizamos a histomorfometria computadorizada para avaliar os túbulos seminíferos e epididimários, considerando as diferentes regiões do epidídimo (cabeça, corpo e cauda) de ratos submetidos a uma dieta prolongada de semente de linhaça. Foram utilizados ratos Wistar machos adultos jovens (n=20) divididos em 2 grupos, durante o período de lactação: Grupo Controle (GC) a base de caseína e Grupo Linhaça (GL) alimentados com 25% de semente de linhaça. Ao final de 250 dias de ingestão contínua, os animais foram sacrificados e amostra de sangue foi coletada. Os testículos e epidídimos foram retirados e fixados em formol tamponado. As amostras foram submetidas ao processamento histológico de rotina para parafina e coradas em hematoxilina e eosina. Foi feita a imunomarcação com anticorpo antivimentina para identificação das células de Sertoli. Para morfometria, as imagens das lâminas foram digitalizadas e analisadas pelo software ImageJ para obtenção dos dados de altura epitelial, diâmetro e área tubular e luminal. Na avaliação hormonal o GL teve maior concentração de estrógeno sérico (p=0,001), mas nenhuma mudança na concentração de testosterona foi observada. Nos parâmetros morfométricos dos túbulos seminíferos e das regiões epididimárias, não houve diferenças significativas entre os grupos analisados. Da mesma forma, a quantificação das células de Sertoli não apresentaram diferenças significativas no GL (p=0,98). Estes resultados mostraram que o consumo contínuo e prolongado de 25% de semente de linhaça desde período gestacional até 250 dias de idade, mesmo com o aumento significativo nos níveis séricos de estradiol, não exerceram efeitos adversos sobre a estrutura testicular e epididimária, assim como nas células participantes da espermatogênese em ratos.(AU)
Assuntos
Animais , Masculino , Ratos , Sementes , Testículo/anatomia & histologia , Ratos Wistar/anatomia & histologia , Linho/efeitos adversos , Epididimo/anatomia & histologia , Túbulos Seminíferos/anatomia & histologia , Células de Sertoli , Vimentina , Técnicas Histológicas/veterinária , Fitoestrógenos/efeitos adversosRESUMO
Flaxseed is considered a functional food with several health benefits. However, because of its high phytoestrogen content, flaxseed influences hormone metabolism and affects the gonadal biomorphology. In this study, computerized histomorphometry was used to evaluate seminiferous and epididymal tubules, considering the different regions of the epididymis (head, body and tail) of rats subjected to a prolonged diet of flaxseed. Young adult male Wistar rats (n=20) were divided into 2 groups during their lactation period: Control Group (CG), fed casein-based meals and Flaxseed Group (FG), fed a 25% flaxseed meal. After 250 days of continuous ingestion, the animals were euthanized and a blood sample was collected. The testicles and epididymis were removed and fixed in buffered formalin solution. The samples were subjected to routine histological paraffin techniques and stained with hematoxilin and eosin. Immunostaining was performed using an antivimentin antibody for Sertoli cell identification. For morphometry, images of the slides were scanned and analyzed using Image J to determine the epithelial height, tubular and luminal diameter and tubular and luminal area. In the hormonal evaluation, FG had a higher serum concentration of estrogen (P=0.001), but no change was observed in the concentration of testosterone. The morphometric assay of seminiferous tubules and epididymal regions revealed no significant differences between the analyzed groups. Similarly, Sertoli cell quantification showed no significant differences in the FG (P=0.98). These results revealed that the continuous and prolonged intake of 25% flaxseed meals from gestation to 250 days of age, even with a significant increase in serum levels of estradiol, does not exert adverse effects on the testicular and epididymal structure or on the cells participating in the spermatogenesis of rats.(AU)
A semente de linhaça é considerada um alimento funcional com vários efeitos benéficos à saúde. Entretanto, devido ao seu elevado teor de fitoestrógenos, esta semente pode influenciar no metabolismo hormonal e interferir na biomorfologia gonadal. Neste estudo, utilizamos a histomorfometria computadorizada para avaliar os túbulos seminíferos e epididimários, considerando as diferentes regiões do epidídimo (cabeça, corpo e cauda) de ratos submetidos a uma dieta prolongada de semente de linhaça. Foram utilizados ratos Wistar machos adultos jovens (n=20) divididos em 2 grupos, durante o período de lactação: Grupo Controle (GC) a base de caseína e Grupo Linhaça (GL) alimentados com 25% de semente de linhaça. Ao final de 250 dias de ingestão contínua, os animais foram sacrificados e amostra de sangue foi coletada. Os testículos e epidídimos foram retirados e fixados em formol tamponado. As amostras foram submetidas ao processamento histológico de rotina para parafina e coradas em hematoxilina e eosina. Foi feita a imunomarcação com anticorpo antivimentina para identificação das células de Sertoli. Para morfometria, as imagens das lâminas foram digitalizadas e analisadas pelo software ImageJ para obtenção dos dados de altura epitelial, diâmetro e área tubular e luminal. Na avaliação hormonal o GL teve maior concentração de estrógeno sérico (p=0,001), mas nenhuma mudança na concentração de testosterona foi observada. Nos parâmetros morfométricos dos túbulos seminíferos e das regiões epididimárias, não houve diferenças significativas entre os grupos analisados. Da mesma forma, a quantificação das células de Sertoli não apresentaram diferenças significativas no GL (p=0,98). Estes resultados mostraram que o consumo contínuo e prolongado de 25% de semente de linhaça desde período gestacional até 250 dias de idade, mesmo com o aumento significativo nos níveis séricos de estradiol, não exerceram efeitos adversos sobre a estrutura testicular e epididimária, assim como nas células participantes da espermatogênese em ratos.(AU)
Assuntos
Animais , Masculino , Ratos , Sementes , Testículo/anatomia & histologia , Ratos Wistar/anatomia & histologia , Linho/efeitos adversos , Epididimo/anatomia & histologia , Túbulos Seminíferos/anatomia & histologia , Células de Sertoli , Vimentina , Técnicas Histológicas/veterinária , Fitoestrógenos/efeitos adversosRESUMO
Dietary soy is thought to be cancer-preventive; however, the beneficial effects of soy on established breast cancer is controversial. We recently demonstrated that dietary daidzein or combined soy isoflavones (genistein, daidzein, and glycitein) increased primary mammary tumor growth and metastasis. Cancer-promoting molecules, including eukaryotic protein synthesis initiation factors (eIF) eIF4G and eIF4E, were up-regulated in mammary tumors from mice that received dietary daidzein. Herein, we show that increased eIF expression in tumor extracts of mice after daidzein diets is associated with protein expression of mRNAs with internal ribosome entry sites (IRES) that are sensitive to eIF4E and eIF4G levels. Results with metastatic cancer cell lines show that some of the effects of daidzein in vivo can be recapitulated by the daidzein metabolite equol. In vitro, equol, but not daidzein, up-regulated eIF4G without affecting eIF4E or its regulator, 4E-binding protein (4E-BP), levels. Equol also increased metastatic cancer cell viability. Equol specifically increased the protein expression of IRES containing cell survival and proliferation-promoting molecules and up-regulated gene and protein expression of the transcription factor c-Myc. Moreover, equol increased the polysomal association of mRNAs for p 120 catenin and eIF4G. The elevated eIF4G in response to equol was not associated with eIF4E or 4E-binding protein in 5' cap co-capture assays or co-immunoprecipitations. In dual luciferase assays, IRES-dependent protein synthesis was increased by equol. Therefore, up-regulation of eIF4G by equol may result in increased translation of pro-cancer mRNAs with IRESs and, thus, promote cancer malignancy.
Assuntos
Neoplasias da Mama/metabolismo , Equol/efeitos adversos , Fator de Iniciação Eucariótico 4G/biossíntese , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glycine max/química , Fitoestrógenos/efeitos adversos , Biossíntese de Proteínas/efeitos dos fármacos , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Suplementos Nutricionais/efeitos adversos , Equol/química , Equol/farmacologia , Fator de Iniciação 4E em Eucariotos/biossíntese , Fator de Iniciação 4E em Eucariotos/genética , Fator de Iniciação Eucariótico 4G/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Isoflavonas/efeitos adversos , Isoflavonas/farmacologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fitoestrógenos/química , Fitoestrógenos/farmacologia , Biossíntese de Proteínas/genética , Proteínas Proto-Oncogênicas c-myc/biossíntese , Proteínas Proto-Oncogênicas c-myc/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Transplante Heterólogo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
The objective of this study was to evaluate the efficacy of flaxseed meal and flaxseed extract in reducing climacteric symptoms of menopausal women. Ninety menopausal women were randomly distributed into three study groups: group I received 1 g per day of flaxseed extract containing at least 100 mg of secoisolariciresinol diglucoside (SDG), group II received 90 g per day of flaxseed meal containing at least 270 mg of SDG, and group III received 1 g per day of collagen (placebo group). Subjects were assessed for menopausal symptoms by the Kupperman index at the beginning and at the end of the 6 months of treatment. Subjects were also assessed for endometrial thickness and vaginal cytology. The Kupperman index values at the beginning and end of the treatments were analyzed using the paired t-test. Both the flaxseed extract (P=.007) and the flaxseed meal (P=.005) were effective in reducing the menopausal symptoms when compared with the placebo control (P=.082). Alternatively, the changes in Kupperman index were also computed and submitted to analysis of variance. In this case, no significant differences were found (P=.084) although the data indicate a decreasing tendency for the Kupperman index by both the flaxseed extract and the flaxseed meal groups. Neither the flaxseed extract nor the flaxseed meal exerted clinically important estrogenic effects on the vaginal epithelium or endometrium as revealed by the absence of changes in the blood levels of follicle stimulating hormone and estradiol, as well as in the endometrial thickness, and vaginal epithelial maturation value. No serious adverse events related to the treatments were reported. Although the results of the present study do not allow an unequivocal conclusion about the action of flaxseed on the menopausal symptoms, they suggest that it could be premature to conclude that no such action exists. Clearly the matter still deserves further experimental attention.
Assuntos
Suplementos Nutricionais , Linho/química , Fogachos/prevenção & controle , Menopausa , Extratos Vegetais/uso terapêutico , Sementes/química , Idoso , Brasil , Butileno Glicóis/administração & dosagem , Butileno Glicóis/efeitos adversos , Butileno Glicóis/análise , Butileno Glicóis/uso terapêutico , Suplementos Nutricionais/efeitos adversos , Endométrio/diagnóstico por imagem , Endométrio/patologia , Células Epiteliais/diagnóstico por imagem , Células Epiteliais/patologia , Estradiol/sangue , Feminino , Linho/efeitos adversos , Hormônio Foliculoestimulante Humano/sangue , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Glucosídeos/análise , Glucosídeos/uso terapêutico , Fogachos/fisiopatologia , Humanos , Hipertrofia , Menopausa/sangue , Pessoa de Meia-Idade , Fitoestrógenos/administração & dosagem , Fitoestrógenos/efeitos adversos , Fitoestrógenos/análise , Fitoestrógenos/uso terapêutico , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Sementes/efeitos adversos , Índice de Gravidade de Doença , Ultrassonografia , Vagina/diagnóstico por imagem , Vagina/patologiaRESUMO
OBJECTIVE: Outcomes from the Women's Health Initiative have demonstrated adverse effects associated with hormone therapy and have prioritized the need to develop new alternative treatments for the management of menopause and osteoporosis. To this end, we have been investigating natural herbal medicines used by Costa Rican women to manage menopausal symptoms. METHODS: Seventeen plant species were collected and extracted in Costa Rica. To establish possible mechanisms of action and to determine their potential future use for menopause or osteoporosis, we investigated the estrogenic activities of the herbal extracts in an estrogen-reporter gene estrogen receptor (ER) beta-Chemically Activated Luciferase Expression assay in U2-OS cells and in reporter and endogenous gene assays in MCF-7 cells. RESULTS: Six of the plant extracts bound to the ERs. Four of the six extracts stimulated reporter gene expression in the ER-beta-Chemically Activated Luciferase Expression assay. All six extracts modulated expression of endogenous genes in MCF-7 cells, with four extracts acting as estrogen agonists and two extracts, Pimenta dioica and Smilax domingensis, acting as partial agonist/antagonists by enhancing estradiol-stimulated pS2 mRNA expression but reducing estradiol-stimulated PR and PTGES mRNA expression. Both P. dioica and S. domingensis induced a 2ERE-luciferase reporter gene in transient transfected MCF-7 cells, which was inhibited by the ER antagonist ICI 182,780. CONCLUSIONS: This work presents a plausible mechanism of action for many of the herbal medicines used by Costa Rican women to treat menopausal symptoms. However, it further suggests that studies of safety and efficacy are needed before these herbs should be used as alternative therapies to hormone therapy.
Assuntos
Menopausa/efeitos dos fármacos , Fitoestrógenos/administração & dosagem , Fitoterapia , Extratos Vegetais/administração & dosagem , Ligação Competitiva , Neoplasias da Mama , Linhagem Celular Tumoral , Costa Rica , Estradiol/análogos & derivados , Estradiol/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/antagonistas & inibidores , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Fulvestranto , Expressão Gênica/efeitos dos fármacos , Genes Reporter/genética , Humanos , Oxirredutases Intramoleculares/genética , Luciferases/genética , Fitoestrógenos/efeitos adversos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/metabolismo , Prostaglandina-E Sintases , RNA Mensageiro/análise , Receptores de Progesterona/genética , Transfecção , Fator Trefoil-1 , Proteínas Supressoras de Tumor/genéticaRESUMO
The use of Hormone Replacement Therapy (HRT) has evolved from a massive utilization to a restricted use under very precise medical indications, in the light of the deletereous effects its indiscriminate prescription could entail. It is not beneficial for secondary prevention, but rather implies additional cardiocerebrovascular risks, and therefore it must be preferentially employed during perimenopausic and non-late periods, in the smallest possible dose and only over short periods of time, restricting its prescription to women presenting with severe estrogen deprivation syndrome or to osteoporotic patients intolerant to calcium and bifosfonates therapy. Breast cancer risk -which is low- is related to a estrogen therapy extended for more than seven years or associated with the use of progesterone for a period exceeding five years. Personal medical records of breast cancer imply absolute contraindication. Currently there are no research work supporting the safe use of phytoestrogens as an alternative therapy. It is likely that in upcoming days transdermal estrogen administration associated with natural progesterone could allow an increased use of them, but for the time being there are no massive studies supporting their recommendation.
El uso de terapia de reemplazo hormonal ha evolucionado desde su empleo masivo a un uso restringido bajo indicaciones precisas, a la luz de los efectos deletéreos que pudiera significar su indicación indiscriminada. No es de utilidad en la prevención secundaria y más bien representa riesgos adicionales cardiovasculares y cerebro vasculares, por lo que se debe emplear de preferencia en el periodo peri-menopáusico y no tardío, en la menor dosis posible y por el menor tiempo necesario, restringiendo su indicación a las mujeres con síntomas de deprivación estrogénica severa o a mujeres osteoporóticas que no toleran la terapia de calcio y bifosfonatos. El riesgo de cáncer de mama -que es bajo- está relacionado con una terapia estrogénica prolongada de 7 años o más o en asociación con el empleo de progesterona por más de 5 años. Antecedentes personales de cáncer de mama representan una contraindicación absoluta. No hay trabajos a la fecha que apoyen el empleo sin riesgo de fitoestrógenos como una terapia alternativa al uso de estrógenos. Es posible que en el futuro la administración transdérmica de los estrógenos, asociado a progesteronas naturales permitan su mayor utilización, pero aún no se dispone de estudios masivos que aprueben su recomendación.
Assuntos
Humanos , Feminino , Fitoestrógenos/administração & dosagem , Neoplasias da Mama/induzido quimicamente , Terapia de Reposição Hormonal/efeitos adversos , Fitoestrógenos/efeitos adversos , Menopausa , Neoplasias da Mama/prevenção & controleRESUMO
Precocious thelarche is the breast development before 8 years of age with two peaks of incidence during the first two years of life and after 6 years of age. A 4.75-year-old girl presented with thelarche associated to an excessive intake of phytoestrogens (phye). Tanner development B2P1-2, hormonal levels and pelvic US were compatible with peripheral precocious puberty. During follow-up, a daily intake of soy-based foods was observed (> 40 mg phye/day). Soy is rich in phytoestrogens, mainly genistein and daidzein. Although phye are less strong than estradiol, its concentration could be from 13,000 to 22,000 times stronger in children fed only by soy-based formulas. Parents were advised and soy intake was reduced to once a week. Progression of pubertal development ceased at B2-3P1. The patient, now 8.66 years old, keeps growing with similar bone and chronological ages. Some questions related to industrial food security, mainly the soy-based food, remain without precise answer. Although it is well known the entity of non-progressive precocious puberty and premature thelarche, pubertal development in this case was strongly related to excessive daily intake of soy and other phye-rich food that could trigger puberty as endocrine disruptor.
Assuntos
Mama/crescimento & desenvolvimento , Fitoestrógenos/efeitos adversos , Puberdade Precoce/induzido quimicamente , Alimentos de Soja/efeitos adversos , Mama/efeitos dos fármacos , Pré-Escolar , Disruptores Endócrinos/efeitos adversos , Feminino , Humanos , Fitoestrógenos/administração & dosagem , Glycine maxRESUMO
Different perturbations during fetal and postnatal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming." Endocrine disruptor compounds (EDC) are widely spread in the environment and display estrogenic, anti-estrogenic or anti-androgenic activity; they are lipophilic and stored for long periods in the adipose tissue. Maternal exposure to EDC during pregnancy and lactation produces the exposure of the fetus and neonate through placenta and breast milk. Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC. Diethystilbestrol (DES) is the best documented compound, this synthetic estrogen was administered to pregnant women in the 1950s and 1960s to prevent miscarriage. It was implicated in urogenital abnormalities in children exposed in utero and was withdrawn from the market. The "DES daughters" are women with high incidence of vaginal hypoplasia, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. The "DES sons" show testicular dysgenesis syndrome, which is characterized by hypospadias, cryptorchidism and low semen quality. This entity is also associated wtih fetal exposure to anti-androgens as flutamide. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of EDC into the environment affects both human health and ecosystems in general, the study of their mechanisms of action is extremely important currently.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Disruptores Endócrinos/efeitos adversos , Genitália/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Anormalidades Induzidas por Medicamentos/epidemiologia , Adulto , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/farmacologia , Animais , Mama/embriologia , Dietilestilbestrol/efeitos adversos , Dietilestilbestrol/farmacologia , Dietilestilbestrol/uso terapêutico , Dioxinas/efeitos adversos , Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/farmacologia , Antagonistas de Estrogênios/efeitos adversos , Antagonistas de Estrogênios/farmacologia , Estrogênios/agonistas , Feminino , Feminização/induzido quimicamente , Feminização/embriologia , Genitália/anormalidades , Genitália/embriologia , Humanos , Hipotálamo/anormalidades , Hipotálamo/efeitos dos fármacos , Hipotálamo/embriologia , Masculino , Glândulas Mamárias Animais/embriologia , Leite Humano/química , Ácidos Ftálicos/efeitos adversos , Fitoestrógenos/efeitos adversos , Fitoestrógenos/farmacologia , Fitoestrógenos/uso terapêutico , Gravidez , Ratos , Virilismo/induzido quimicamente , Virilismo/embriologiaRESUMO
Telarca precoce, desenvolvimento mamário antes dos 8 anos de idade, apresenta dois picos de incidência, nos dois primeiros anos de vida e após os 6 anos de idade. Uma menina de 4,75 anos apresentou-se com telarca associada à ingestão excessiva de fitoestrógenos. O desenvolvimento puberal M2P1-2, os níveis hormonais e o US pélvico eram compatíveis com puberdade precoce periférica. Durante o seguimento, observou-se ingestão diária de alimentos baseados em soja (> 40 mg fitoestrógenos/dia). Soja contém fitoestrógenos, principalmente genisteína e daidzeína. Embora menos potentes do que o estradiol, sua concentração pode ser 13.000 a 22.000 vezes maior em crianças alimentadas somente com fórmulas baseadas em soja. Os pais foram aconselhados a reduzir para uma vez na semana o seu fornecimento na dieta. O desenvolvimento puberal cessou em M2-3P1 e a paciente, com 8,66 anos, continua a desenvolver-se com idades óssea e cronológica equivalentes. Questões relacionadas à segurança alimentar, principalmente de alimentos baseados em soja, permanecem sem respostas precisas. Embora sejam conhecidas as etiologias da puberdade precoce não progressiva e da telarca prematura, neste caso esteve fortemente relacionada à ingestão excessiva de soja e de outros alimentos ricos em fitoestrógenos que poderiam ter desencadeado a telarca atuando como desreguladores endócrinos.
Precocious thelarche is the breast development before 8 years of age with two peaks of incidence during the first two years of life and after 6 years of age. A 4.75-year-old girl presented with thelarche associated to an excessive intake of phytoestrogens (phye). Tanner development B2P1-2, hormonal levels and pelvic US were compatible with peripheral precocious puberty. During follow-up, a daily intake of soy-based foods was observed (> 40 mg phye/day). Soy is rich in phytoestrogens, mainly genistein and daidzein. Although phye are less strong than estradiol, its concentration could be from 13,000 to 22,000 times stronger in children fed only by soy-based formulas. Parents were advised and soy intake was reduced to once a week. Progression of pubertal development ceased at B2-3P1. The patient, now 8.66 years old, keeps growing with similar bone and chronological ages. Some questions related to industrial food security, mainly the soy-based food, remain without precise answer. Although it is well known the entity of non-progressive precocious puberty and premature thelarche, pubertal development in this case was strongly related to excessive daily intake of soy and other phye-rich food that could trigger puberty as endocrine disruptor.
Assuntos
Pré-Escolar , Feminino , Humanos , Mama/crescimento & desenvolvimento , Fitoestrógenos/efeitos adversos , Puberdade Precoce/induzido quimicamente , Alimentos de Soja/efeitos adversos , Mama/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Fitoestrógenos/administração & dosagem , Glycine maxRESUMO
Different perturbations during fetal and post natal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming"'. Endocrine disruptor compounds (EDC) are widely spread on the environment and display estrogenic, anti-estrogenic or anti-androgenic activity; they are lypophilyc and stored for long periods on the adipose tissue. Maternal exposure to EDC during pregnancy and lactation produces the exposure of the fetus and neonate through placenta and breast milk. Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC. Diethystilbestrol (DES) is the best documented compound, this synthetic estrogen was administered to pregnant women at the BO and 60 to prevent miscarriage. It was implicated in urogenital abnormalities in children exposed in utero and withdrawn from the market. The "DES daughters" are women with high incidence of vaginal hypoplasia, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. The "DES sons" show testicular dysgenesis syndrome, which is characterized by hypospadias, cryptorchidism and low semen quality. This entity is also associated to the fetal exposure to anti-androgens as flutamide. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of EDC into the environment affects both human health and ecosystems in general, the study of their mechanisms of action is extremely important currently.
Diversas perturbaciones durante el desarrollo fetal y posnatal desencadenan adaptaciones endocrinas que modifican permanentemente el metabolismo, incrementando la susceptibilidad para el desarrollo de enfermedades, proceso conocido como "programación durante el desarrollo". Los compuestos disruptores endocrinos (CDE) se encuentran en el medio ambiente y presentan actividad estrogénica, antiestrogénica o antiandrogénica; son altamente lipofílicos y se almacenan por periodos prolongados en el tejido adiposo. La exposición materna a CDE durante el embarazo y la lactancia permite su paso al producto a través de la placenta y la leche materna. Estudios epidemiológicos y experimentales han demostrado alteraciones en el eje reproductivo como consecuencia de la exposición intrauterina y/o neonatal a CDE. El compuesto mejor documentado es el dietilestilbestrol (DES), este estrógeno sintético fue administrado a mujeres embarazadas durante los 50s y 60s y retirado del mercado por su implicación en anormalidades urogenitales de los bebés expuestos in útero. Las denominadas "hijas del DES" son mujeres con alta incidencia de hipoplasia vaginal, malformaciones uterinas, irregularidades menstruales, baja fertilidad y alta prevalencia de aborto espontáneo y parto prematuro. Por su parte, "los hijos del DES" presentan una entidad clínica conocida como síndrome de disgenesia testicular caracterizado por hipospadias, criptorquidia y baja calidad del semen. Este síndrome también se asocia a la exposición fetal a compuestos antiandrogénicos como la ñutamida. Los efectos en el eje reproductivo dependen del estadio de desarrollo y del tiempo de exposición, así como de la dosis y el compuesto del que se trate. La extensa presencia de CDE en el ambiente afecta la salud humana e impacta al ecosistema en general por lo cual es de suma importancia el estudio de los mecanismos involucrados en su acción.