Comportamento materno e câncer de bexiga urinária: implicações da modulação de eixos hormonais e receptores de esteroides na fisiopatologia de lesões neoplásicas
Carregando...
Data
2016-02-26
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O carcinoma de bexiga urinária é o tipo de câncer mais prevalente no sistema urinário em seres humanos e apresenta altos índices de morbidade e mortalidade. Seu desenvolvimento está relacionado a diversos fatores de risco, como o hábito de fumar, a exposição a agentes químicos industriais e metais pesados e o estresse crônico. As experiências adversas no início da vida estão relacionadas à modulação de eixos hormonais importantes, como o hipotalâmicohipofisário-adrenal (HHA) e hipotalâmico-hipofisário-gonadal (HHG). Alterações na resposta do eixo HHA, componente central da resposta fisiológica ao estresse, levam a desordens fisiológicas, como aumento da proliferação celular, angiogênese e prejuízo da resposta imune, que podem ser responsáveis pelo aumento da susceptibilidade do indivíduo a uma série de doenças na vida adulta, incluindo o câncer. Paralelamente, alterações na fisiologia de hormônios esteroides como andrógenos, estrógenos e glicocorticoides, bem como seus receptores, também têm sido relacionadas ao desenvolvimento de enfermidades como o câncer de bexiga urinária. Em ratos, o comportamento materno funciona como um fator importante na modulação desses eixos hormonais, modificando suas respostas na vida adulta, e estudos recentes têm relacionado os cuidados recebidos por filhotes à incidência de tumores. O objetivo deste estudo foi avaliar a influência do comportamento materno e sua consequente modulação nos eixos HHA e HHG, no desenvolvimento do câncer de bexiga urinária. Os resultados mostraram que ratas criadas por mães negligentes apresentaram maior susceptibilidade ao desenvolvimento do câncer de bexiga urinária induzido quimicamente, pois desenvolveram lesões uroteliais mais graves quando comparadas a fêmeas que receberam cuidados maternos intensos. Também foi observado que os níveis de receptores de hormônios esteroides na bexiga urinária foram sensíveis ao tipo de cuidados recebidos. Desta forma concluímos que o comportamento materno, recebido durante o desenvolvimento pós-natal, influencia o desenvolvimento e a gravidade de tumores uroteliais induzidos quimicamente em roedores, possivelmente através da regulação de níveis hormonais e de receptores de esteroides. Novos estudos são necessários para entender essa relação complexa, principalmente para compreender se os cuidados maternos neonatais são protetores ou se a negligência materna favorece o desenvolvimento de enfermidades graves no adulto, como o carcinoma urotelial.
The urinary bladder carcinoma is the most prevalent type of cancer in the urinary tract in humans, with high morbidity and mortality. Its development is related to several risk factors such as smoking, exposure to industrial chemicals and heavy metals and chronic stress. Adverse experiences early in life are related to modulation of important hormonal axes, as the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG). Changes in the response of the HPA axis, a central component of the physiological response to stress, lead to physiological disorders, such as increased cell proliferation, angiogenesis, and impaired immune response, which may be responsible for the increased susceptibility of the individual to a number of diseases in adult life, including cancer. Similarly, changes in the physiology of steroid hormones such as androgens, oestrogens and glucocorticoids and their receptors have also been related to the development of diseases such as bladder cancer. In rats, maternal behavior serves as an important factor in the modulation of hormonal axes, modifying their responses in adulthood, and recent studies have linked the care received by pups and the incidence of tumors. The aim of this study was to evaluate the influence of maternal behavior and its consequent modulation in HPA and HPG axes in the development of bladder cancer. The results showed that rats reared by the negligent mothers had a greater susceptibility to the development of chemically induced bladder cancer, for urothelial lesions developed more severe when compared to females receiving intense maternal care. It was also observed that the levels of steroid hormone receptors in the urinary bladder were sensitive to the type of care received. Thus we conclude that maternal behavior, received during the postnatal development, influence the development and severity of urothelial chemically induced tumors in rodents, possibly through regulation of hormone levels and steroid receptors. Further studies are needed to understand this complex relationship, especially to understand whether neonatal intensive maternal care is protective or maternal neglect favors the development of serious illnesses in adults, such as urothelial carcinoma.
The urinary bladder carcinoma is the most prevalent type of cancer in the urinary tract in humans, with high morbidity and mortality. Its development is related to several risk factors such as smoking, exposure to industrial chemicals and heavy metals and chronic stress. Adverse experiences early in life are related to modulation of important hormonal axes, as the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG). Changes in the response of the HPA axis, a central component of the physiological response to stress, lead to physiological disorders, such as increased cell proliferation, angiogenesis, and impaired immune response, which may be responsible for the increased susceptibility of the individual to a number of diseases in adult life, including cancer. Similarly, changes in the physiology of steroid hormones such as androgens, oestrogens and glucocorticoids and their receptors have also been related to the development of diseases such as bladder cancer. In rats, maternal behavior serves as an important factor in the modulation of hormonal axes, modifying their responses in adulthood, and recent studies have linked the care received by pups and the incidence of tumors. The aim of this study was to evaluate the influence of maternal behavior and its consequent modulation in HPA and HPG axes in the development of bladder cancer. The results showed that rats reared by the negligent mothers had a greater susceptibility to the development of chemically induced bladder cancer, for urothelial lesions developed more severe when compared to females receiving intense maternal care. It was also observed that the levels of steroid hormone receptors in the urinary bladder were sensitive to the type of care received. Thus we conclude that maternal behavior, received during the postnatal development, influence the development and severity of urothelial chemically induced tumors in rodents, possibly through regulation of hormone levels and steroid receptors. Further studies are needed to understand this complex relationship, especially to understand whether neonatal intensive maternal care is protective or maternal neglect favors the development of serious illnesses in adults, such as urothelial carcinoma.
Descrição
Palavras-chave
Urinary bladder cancer, HPA axis, Stress, MNU, Esteroid receptors