RESUMO
Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 µg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17ß-estradiol (2.0 µg) every fourth day, or a ß-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle changes, decreased high levels of circulating luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high ovarian gene expression of adiponectin receptor 2, and increased expression of adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3, Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further, total bone mineral density was higher in the letrozole-estradiol group. Thus, EA modulates the circulating gonadotropin levels independently of sex steroids or ß-adrenergic action and affects the expression of ovarian adiponectin system.
Assuntos
Adiponectina/metabolismo , Gonadotropinas/sangue , Ovário/metabolismo , Síndrome do Ovário Policístico/sangue , Terapia por Acupuntura , Animais , Densidade Óssea , Modelos Animais de Doenças , Estradiol/sangue , Ciclo Estral , Feminino , Expressão Gênica , Hiperandrogenismo/sangue , Hiperandrogenismo/terapia , Fator de Crescimento Insulin-Like I/metabolismo , Síndrome do Ovário Policístico/terapia , Progesterona/sangue , Ratos Wistar , Receptores Adrenérgicos beta/metabolismo , Testosterona/sangueRESUMO
BACKGROUND: Despite considerable racial and geographical differences in human phenotypes and in the incidence of diseases that may be associated with sex steroid action, there are few data concerning variation in sex steroid levels among populations. We designed an international study to determine the degree to which geography and race influence sex steroid levels in older men. METHODS: Using mass spectrometry, concentrations of serum androgens, estrogens, and sex steroid precursors/metabolites were measured in 5003 older men from five countries. SHBG levels were assessed using radioimmunoassay. RESULTS: There was substantial geographical variation in the levels of sex steroids, precursors, and metabolites, as well as SHBG. For instance, Asian men in Hong Kong and Japan, but not in the United States, had levels of total testosterone approximately 20% higher than in other groups. Even greater variation was present in levels of estradiol, SHBG, and dihydrotestosterone. Group differences in body mass index did not explain most geographical differences. In addition, body mass index-independent racial differences were present; Black men had higher levels of estrogens (estradiol, estrone), and Asian men had lower levels of glucuronidated androgen metabolites. CONCLUSIONS: On a global scale, there are important geographical and racial differences in the concentrations of serum sex steroids and SHBG in older men.
Assuntos
Hormônios Esteroides Gonadais/sangue , Grupos Raciais , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/metabolismo , Análise Química do Sangue/métodos , Estudos de Coortes , Geografia , Hormônios Esteroides Gonadais/análise , Hormônios Esteroides Gonadais/metabolismo , Hong Kong , Humanos , Japão , Masculino , Espectrometria de Massas , Modelos Biológicos , Grupos Raciais/estatística & dados numéricos , Globulina de Ligação a Hormônio Sexual/análise , Globulina de Ligação a Hormônio Sexual/metabolismo , Trinidad e Tobago , Estados UnidosRESUMO
It is clear that all available means should be taken to diagnose prostate cancer early and to use efficient therapy immediately in order to prevent prostate cancer from migrating to the bones where treatment becomes extremely difficult and cure or even long-term control of the disease is an exception. The only means of preventing prostate cancer from migrating to the bones and becoming incurable is efficient treatment at the localized stage of the disease. In fact, since radical prostatectomy, radiotherapy and brachytherapy can achieve cure in about 50 percent of cases, these approaches are all equally valid choices as first treatment of localized prostate cancer. However, in view of the current knowledge and available data, nowadays, androgen blockade should also be considered as first line treatment. While showing the high efficacy of hormonal therapy in localized prostate cancer, present knowledge clearly indicate that long-term treatment with the best available hormonal drugs, somewhat similar to the 5 years of Tamoxifen in breast cancer, is required for optimal control of prostate cancer. It is also clear from the data analyzed that combined androgen blockage alone could well be an efficient therapy of localized prostate cancer while it has already been recognized as the best therapy for metastatic disease. This paper presents and discusses the current knowledge available on the use and results of endocrine therapy in localized prostate cancer.
Assuntos
Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/antagonistas & inibidores , Intervalo Livre de Doença , Prognóstico , Neoplasias da Próstata/cirurgia , Receptores Androgênicos/fisiologiaRESUMO
It is clear that all available means should be taken to diagnose prostate cancer early and to use efficient therapy immediately in order to prevent prostate cancer from migrating to the bones where treatment becomes extremely difficult and cure or even long-term control of the disease is an exception. The only means of preventing prostate cancer from migrating to the bones and becoming incurable is efficient treatment at the localized stage of the disease. In fact, since radical prostatectomy, radiotherapy and brachytherapy can achieve cure in about 50% of cases, these approaches are all equally valid choices as first treatment of localized prostate cancer. However, in view of the current knowledge and available data, nowadays, androgen blockade should also be considered as first line treatment. While showing the high efficacy of hormonal therapy in localized prostate cancer, present knowledge clearly indicate that long-term treatment with the best available hormonal drugs, somewhat similar to the 5 years of Tamoxifen in breast cancer, is required for optimal control of prostate cancer. It is also clear from the data analyzed that combined androgen blockage alone could well be an efficient therapy of localized prostate cancer while it has already been recognized as the best therapy for metastatic disease. This paper presents and discusses the current knowledge available on the use and results of endocrine therapy in localized prostate cancer.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Intervalo Livre de Doença , Humanos , Masculino , Prognóstico , Neoplasias da Próstata/cirurgia , Receptores Androgênicos/fisiologiaRESUMO
Nós estudamos o efeito do tratamento com os esteróides da supra-renais o androstenodiol (delta5-diol) e a dihidroepiandrosterona (DHEA) no crescimento e níveis dos receptores da progesterona em tumores mamários induzidos pelo DMBA nas ratas. Enquanto poucos tumores apareceram nas ratas ooforectomizadas (OOF), (média de 0,60 ñ 0,19/rata) após 24 dias, nas ratas OOF tratadas com delta 5 -diol ou DHEA (2mg, duas vezes por dia), as médias foram 2,54 ñ 0,50 (p < 0,01) e 1,42 ñ 0,26 (p < 0,01) respectivamente. O aparecimento de tumores novos foi muito reduzido nas ratas OOF (0,07 ñ 0,07/rata) durante os 24 dias de observaçäo, com uma média de 0,47 ñ 0,19/rata (p < 0,05) nas ratas intactas. Nas ratas OOF tratadas com delta5-diol ou DHEA o número de tumores novos foram 0,77 ñ 0,26 (p < 0,05) e 0,42 ñ 0,15 (p < 0,05) por animal, respectivamente. Um efeito ainda mais marcante foi observado na área média total dos tumores, os quais decresceram de 4,70 ñ 0,95 cm* nas ratas intactas para 0,75 ñ 0,27 cm* (p < 0,01) após ooforectomia. Valores de 9,79 ñ 2,25 (p < 0,01) e 3,93 ñ 0,86 cm* (p < 0,01) foram encontrados nas ratas OOF tratadas com delta5-diol e DHEA, respectivamente. As ratas OOF tratadas com delta5-diol e DHEA, mostraram um aumento altamente significante (p < 0,01) nos níveis dos receptores da progesterona nos tumores mamários e nos úteros. O peso uterino estava também aumentado (p < 0,01), pelo tratamento com estes dois esteróides das supra-renais. Estes resultados demonstram, pela primeira vez, que os dois esteróides C19 das supra-renais delta5-diol e DHEA, possuem um efeito estimulatório análogo aos dos estrógenos no crescimento e níveis dos receptores da progesterona em tumores mamários induzidos pelo DMBA nas ratas, desta forma comprovando sugestöes do papel importante destes esteróides das supra-renais no câncer de mama e outras patologias estrógeno-sensíveis na espécie humana