Neurotrophic function of erythropoietin

促红细胞生成素（EPO）是一种由成人肾脏产生的糖蛋白。长期以来，人们认为促红细胞生成是促红细胞生成素的唯一生理功能，但我们已经证明，促红细胞生成素在大脑中产生，并保护神经元免受缺血性损伤。这一发现得到了随后发表的许多论文的支持，重组人类促生成素将作为治疗各种脑部疾病的方法进行研究。缺氧显著增强EPO基因的表达。EPO基因在肾和脑中的表达都是缺氧诱导的，但表达模式有很大不同。当动物暴露于缺氧（7%氧气）时，暴露后4小时两个器官的EPO mRNA增加40-80倍。EPO mRNA在动物缺氧条件下保持高水平。虽然机制尚不清楚，但这一发现暗示了生理学上的重要性：(1)肾脏EPO mRNA的持续高水平引起红细胞增多，导致各种血管疾病，因此肾中的EPO mRNA必须在缺氧的情况下降低；(2)大脑中的EPO是缺氧条件下神经保护所必需的，因此在缺氧时持续高水平。我们已经证明EPO也在子宫中产生，EPO作为子宫内膜周期性生长的血管生成因子。子宫内促生成素的产生也是缺氧诱导的，但促生成素的缺氧诱导需要雌激素。

Erythropoietin (EPO) is a glycoprotein that is produced by the kidney in adults. It has been belived for long time that stimulation of erythropoiesis is a sole physiological function of EPO but we have demonstrated that EPO is produced in brain and protects neurons from ischemic damage. This finding has been supported by a number of papers subsequently publised and recombinant human EPO is going to be examined as a therapeutic of various brain diseases.Expression of EPO gene is markedly enhanced by hypoxia. Expression of EPO gene in both kidney and brain is hypoxia-inducible but the expression patterns are quite different. When animals are exposed to hypoxia (7 % oxygen), EPO mRNA in both organs increases 40-80-fold at 4 hr after exposure. EPO mRNA is kept at a high level as far as animals are exposed to hypoxia. Although the mechanism remains unknown, this finding implicates the physiological importance that (1) the continuous high level of the kidney EPO mRNA causes erthrocytosis, leading to various vascular disorders and therefore EPO mRNA in the kidney must be decreased despite of hypoxia and that (2) EPO in the brain is required for neuroprotection under hyoxia and therefore a high level continues during hypoxia.We have shown that EPO is also produced in the uterus where EPO acts as an angiogenic factor for periodical growth of uterine endometrial layer. EPO production in the uterus is also hypoxia-inducible but estrogen is required for hypoxic induction of EPO.