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首页> 外文期刊>Endocrinology >The differences in neuroprotective efficacy of progesterone and medroxyprogesterone acetate correlate with their effects on brain-derived neurotrophic factor expression.
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The differences in neuroprotective efficacy of progesterone and medroxyprogesterone acetate correlate with their effects on brain-derived neurotrophic factor expression.

机译：孕酮和醋酸甲羟孕酮在神经保护功效上的差异与其对脑源性神经营养因子表达的影响有关。

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Whereas hormone therapy is used for the treatment of menopausal symptoms, its efficacy in helping reduce the risk of other diseases such as Alzheimer's disease has been questioned in view of the results of recent clinical trials that appeared inconsistent with numerous basic research studies that supported the beneficial effects of hormones. One possible explanation of this discrepancy may lie in the choice of hormone used. For example, we and others found that progesterone is neuroprotective whereas medroxyprogesterone acetate (MPA), the synthetic progestin used in hormone therapy, is not. Because our data suggest that progesterone-induced protection is associated with the induction of brain-derived neurotrophic factor (BDNF) levels and, importantly, can be blocked by inhibiting the neurotrophin signaling, we determined whether progesterone and medroxyprogesterone acetate differed in their ability to regulate BDNF levels in the explants of the cerebral cortex. We found that progesterone elicited an increase in both BDNF mRNA and protein levels, whereas medroxyprogesterone acetate did not. Furthermore, using both a pharmacological inhibitor of the progesterone receptor (PR) and PR knockout mice, we determined that the effects of progesterone were mediated by the classical PR. Our results underscore the fact that not all progestins have equivalent effects on the brain and suggest that the selection of the appropriate progestin may influence the success of hormone therapy formulations used in treating the menopause and/or reducing the risk for diseases associated with the postmenopausal period.
机译：尽管激素疗法可用于治疗更年期症状，但鉴于最近的临床试验结果与众多支持有益研究的基础研究不一致，因此人们对激素疗法在降低其他疾病如阿尔茨海默氏病风险方面的功效提出了质疑。激素的影响。这种差异的一种可能解释可能是所用激素的选择。例如，我们和其他人发现，孕酮具有神经保护作用，而醋酸甲羟孕酮（MPA）（用于激素治疗的合成孕激素）则没有神经保护作用。因为我们的数据表明孕酮诱导的保护与诱导脑源性神经营养因子（BDNF）水平相关，并且重要的是可以通过抑制神经营养因子信号传导来阻断，因此我们确定了孕酮和乙酸甲羟孕酮在调节能力上是否不同大脑皮层外植体中的BDNF水平。我们发现黄体酮引起BDNF mRNA和蛋白质水平的增加，而醋酸甲羟孕酮却没有。此外，我们同时使用孕激素受体（PR）和PR基因敲除小鼠的药理抑制剂，我们确定孕激素的作用是由经典PR介导的。我们的结果强调了并非所有孕激素对大脑都有同等作用的事实，并表明选择合适的孕激素可能会影响用于治疗更年期的激素治疗制剂的成功和/或降低绝经后相关疾病的风险。

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