Although human cultures stimulated with dexamethasone suggest that the glucocorticoid receptor (GR) activates stress erythropoiesis, the effects of GR activation on erythropoiesis in vivo remains poorly understood. We characterized the phenotype of a large cohort of patients with Cushing's Disease, a rare condition associated with elevated cortisol levels. Results from hypercortisolemic patients with active Cushing's were compared with those obtained from eucortisolemic patients after remission and from non-diseased volunteers. Active Cushing's patients exhibit erythrocytosis associated with normal hemoglobin F levels. In addition, their blood contained elevated numbers of the GR-induced CD163+ monocytes and a unique class of CD34+ cells expressing CD110, CD36, CD133 and the GR-target gene CXCR4. When cultured, these CD34+ cells generated similarly large numbers of immature erythroid cells in the presence and absence of dexamethasone, with raised expression of the GR-target gene GILZ. Of interest, blood from Cushing's patients in remission maintained high numbers of CD163+ monocytes and, although their CD34+ cells had a normal phenotype, these cells were unresponsive to added dexamethasone. Collectively, these results indicate that chronic exposure to excess glucocorticoids in vivo leads to erythrocytosis by generating erythroid progenitor cells with a constitutively active GR. Although remission rescues the erythrocytosis and the phenotype of the circulating CD34+ cells, a memory of other prior changes is maintained in remission.

中文翻译：

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高皮质醇血症库欣患者拥有一类独特的造血祖细胞，导致红细胞增多。

尽管用地塞米松刺激的人类培养物表明糖皮质激素受体 (GR) 激活应激性红细胞生成，但 GR 激活对体内红细胞生成的影响仍知之甚少。我们对一大群库欣病患者的表型进行了表征，库欣病是一种与皮质醇水平升高相关的罕见疾病。将患有活动性库欣病的高皮质醇血症患者的结果与缓解后的正常皮质醇血症患者以及未患病志愿者的结果进行比较。活性库欣病患者表现出与正常血红蛋白 F 水平相关的红细胞增多症。此外，他们的血液中含有大量 GR 诱导的 CD163+ 单核细胞和一类独特的 CD34+ 细胞，表达 CD110、CD36、CD133 和 GR 靶基因 CXCR4。培养时，无论是否存在地塞米松，这些 CD34+ 细胞都会产生类似大量的未成熟红系细胞，并且 GR 靶基因 GILZ 的表达升高。有趣的是，库欣缓解期患者的血液中维持了大量的 CD163+ 单核细胞，尽管他们的 CD34+ 细胞具有正常表型，但这些细胞对添加的地塞米松没有反应。总的来说，这些结果表明，体内长期暴露于过量糖皮质激素，通过产生具有组成型活性GR的红系祖细胞，导致红细胞增多。尽管缓解可挽救红细胞增多症和循环 CD34+ 细胞的表型，但缓解期间仍保留对其他先前变化的记忆。