Strom Jakob O, Theodorsson Annette, Theodorsson Elvar
Institution of Clinical and Experimental Medicine/Department of Clinical Chemistry, Linkoping University, Linkoping, Sweden.
Institution of Clinical and Experimental Medicine/Department of Neurosurgery, Linkoping University, Linkoping, Sweden.
Pharmaceuticals (Basel). 2011 May 16;4(5):726-740. doi: 10.3390/ph4050726.
Hormone replacement after menopause has in recent years been the subject of intense scientific debate and public interest and has sparked intense research efforts into the biological effects of estrogens and progestagens. However, there are reasons to believe that the doses used and plasma concentrations produced in a large number of studies casts doubt on important aspects of their validity. The concept of hormesis states that a substance can have diametrically different effects depending on the concentration. Even though estrogens and progestagens have proven prone to this kind of dose-response relation in a multitude of studies, the phenomenon remains clearly underappreciated as exemplified by the fact that it is common practice to only use one hormone dose in animal experiments. If care is not taken to adjust the concentrations of estrogens and progestagens to relevant biological conditions, the significance of the results may be questionable. Our aim is to review examples of female sexual steroids demonstrating bidirectional dose-response relations and to discuss this in the perspective of hormesis. Some examples are highlighted in detail, including the effects on cerebral ischemia, inflammation, cardiovascular diseases and anxiety. Hopefully, better understanding of the hormesis phenomenon may result in improved future designs of studies of female sexual steroids.
近年来，绝经后的激素替代一直是激烈科学辩论和公众关注的主题，并引发了对雌激素和孕激素生物学效应的深入研究。然而，有理由相信，大量研究中使用的剂量和产生的血浆浓度对其有效性的重要方面存在疑问。毒物兴奋效应的概念表明，一种物质根据浓度不同可能产生截然相反的效果。尽管在众多研究中已证明雌激素和孕激素容易出现这种剂量反应关系，但这一现象仍明显未得到充分认识，例如在动物实验中通常只使用一种激素剂量这一事实就说明了这一点。如果不注意将雌激素和孕激素的浓度调整到相关生物学条件，结果的意义可能存疑。我们的目的是回顾显示双向剂量反应关系的女性性甾体激素的例子，并从毒物兴奋效应的角度进行讨论。详细突出了一些例子，包括对脑缺血、炎症、心血管疾病和焦虑的影响。希望对毒物兴奋效应现象的更好理解可能会改进未来女性性甾体激素研究的设计。
