The effects of iron deficiency on estradiol-induced suppression of erythropoietin induction in rats: implications of pregnancy-related anemia
The effects of iron deficiency on estradiol-induced suppression of erythropoietin induction in rats: implications of pregnancy-related anemia
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DOI：
10.1182/blood-2004-06-2350
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发表时间：
2005-07-01
期刊：
影响因子：
20.3
通讯作者：
Kayama, F
中科院分区：
文献类型：
--
作者：
Horiguchi, H;Oguma, E;Kayama, F
妊娠妇女常伴随着血清促红细胞生成素水平的升高而发生贫血，而实际上血清促红细胞生成素水平低于非妊娠贫血妇女，这是因为内源性雌二醇可能抑制了促红细胞生成素的诱导。贫血源于血液稀释，并不是促红细胞生成素诱导的动力，但通常在怀孕期间观察到的铁缺乏可能会促使促红细胞生成素的产生。为了证明这一点，我们研究了缺铁对雌激素诱导的大鼠促红细胞生成素诱导的抑制的影响。单剂量雌二醇抑制低氧、钴和出血刺激的血浆促红细胞生成素水平和肾脏促红细胞生成素mRNA的表达。重复给予雌二醇0.1和1 mg/kg 2个月，可引起轻微的贫血倾向，但血浆促红细胞生成素未见升高。低铁饲料喂养2个月后，大鼠血浆促红细胞生成素水平升高，未见明显贫血，但同时重复给予雌二醇可抑制血浆促红细胞生成素升高，逆转铁缺乏状态。血浆促红细胞生成素水平与血浆铁、血浆铁蛋白和器官中铁浓度呈显著负相关，而与血浆血红蛋白水平无相关性。这些结果表明，缺铁会显著刺激孕期促红细胞生成素的诱导，尽管雌二醇可能通过铁恢复抑制促红细胞生成素的诱导。
Pregnant women often develop anemia concomitant with the increase in serum erythropoietin levels, which are actually lower than those of nonpregnant anemic women due to the possible suppressive effect of endogenous estradiol on erythropoietin induction. The anemia, derived from hemodilution, does not act as a drive for erythropoietin induction, but iron deficiency, often observed during pregnancy, might. In order to demonstrate this, we investigated the effects of iron deficiency on estradiol-induced suppression of erythropoietin induction in rats. Single doses of estradiol suppressed hypoxia-, cobalt-, and bleeding-stimulated elevation of plasma erythropoietin levels and renal erythropoietin mRNA expression. Repeated administration of estradiol at 0.1 and 1 mg/kg for 2 months induced a slight anemic trend without elevation of plasma erythropoietin. Feeding an iron-deficient diet for 2 months induced plasma erythropoietin elevation without obvious anemia, but the simultaneous repeated administration of estradiol suppressed it and reversed the iron deficiency. Plasma erythropoietin levels had distinct negative correlations with plasma iron, plasma ferritin, and iron concentrations in the organs, but not with plasma hemoglobin level. These results suggest that iron deficiency would significantly stimulate erythropoietin induction during pregnancy, although estradiol might suppress it through iron restoration.