Department of Physiology, Pomeranian Medical University, 72 Powstancow Wlkp Street, 70-111 Szczecin, Poland.
Eur J Endocrinol. 2010 Feb;162(2):295-305. doi: 10.1530/EJE-09-0875. Epub 2009 Nov 10.
Abnormalities in haematological parameters have been noted in patients with thyroid diseases. Nevertheless, the exact mechanism of thyroid hormones' (THs) action on human haematopoiesis is still not entirely clear.
The influence of THs through TH receptors (TRalpha-1 and TRbeta-1) on haematopoiesis in patients with hypo- and hyperthyroidism was analysed.
TR gene expression at the mRNA and protein levels in human CD34(+)-enriched haematopoietic progenitor cells (HPCs) obtained from the peripheral blood of patients with thyroid disorders and healthy volunteers was analysed. The cell populations were also investigated for clonogenic growth of granulocyte macrophage-colony forming units and erythrocyte-burst forming units (BFU-E). The level of apoptosis was determined by annexin V/propidium iodide staining and quantitative RT-PCR.
The studies revealed that hypo- and hyperthyroidism modify TR gene expression in HPCs in vivo. TH deficiency resulted in a decrease in total blood counts and clonogenic potential of BFU-E. In contrast, hyperthyroid patients presented increased clonogenic growth and BFU-E number and significantly higher expressions of cell cycle-regulating genes such as those for PCNA and cyclin D1. Finally, an increase in the frequency of apoptotic CD34(+)-enriched HPCs in hypo- and hyperthyroidism with a modulation of apoptosis-related genes was detected.
The following conclusions were derived: i) TR expression in human haematopoietic cells depends on TH status, ii) both hypo- and hyperthyroidism significantly influence clonogenicity and induce apoptosis in CD34(+)-enriched HPCs and iii) the molecular mechanism by which THs influence haematopoiesis might provide a basis for designing novel therapeutic interventions in thyroid diseases.
甲状腺疾病患者的血液学参数常出现异常。然而，甲状腺激素（THs）对人类造血作用的确切机制仍不完全清楚。
分析甲状腺功能减退症和甲状腺功能亢进症患者中 TH 通过 TH 受体（TRalpha-1 和 TRbeta-1）对造血的影响。
分析来自甲状腺功能紊乱患者和健康志愿者外周血的 CD34(+)富集造血祖细胞（HPC）中 TR 基因在 mRNA 和蛋白水平的表达。还研究了细胞群体粒细胞巨噬细胞集落形成单位和红细胞爆式集落形成单位（BFU-E）的克隆生长情况。通过 Annexin V/碘化丙啶染色和定量 RT-PCR 测定细胞凋亡水平。
研究表明，甲状腺功能减退症和甲状腺功能亢进症改变了 HPC 中 TR 基因的表达。TH 缺乏导致全血细胞计数和 BFU-E 的集落形成潜力降低。相反，甲状腺功能亢进症患者表现出集落生长和 BFU-E 数量增加，以及细胞周期调节基因（如 PCNA 和 cyclin D1）的表达显著增加。最后，在甲状腺功能减退症和甲状腺功能亢进症中检测到 CD34(+)富集 HPC 中凋亡频率增加，并调节了与凋亡相关的基因。
得出以下结论：i）TH 状态决定了人类造血细胞中 TR 的表达，ii）甲状腺功能减退症和甲状腺功能亢进症均显著影响 CD34(+)富集 HPC 的集落生成，并诱导其凋亡，iii）TH 影响造血的分子机制可能为设计甲状腺疾病的新型治疗干预提供依据。
