Clinical relevance of thyroid dysfunction in human haematopoiesis: biochemical and molecular studies

Abstract

Objective: 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. Design: The influence of THs through TH receptors (TRa-1 and TRb-1) on haematopoiesis in patients with hypo-and hyperthyroidism was analysed. Methods: TR gene expression at the mRNA and protein levels in human CD34C -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. Results: 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 CD34C -enriched HPCs in hypo-and hyperthyroidism with a modulation of apoptosis-related genes was detected. Conclusions: 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 C -enriched HPCs and iii) the molecular mechanism by which THs influence haematopoiesis might provide a basis for designing novel therapeutic interventions in thyroid diseases.

A high concentration of triiodothyronine attenuates the stimulatory effect on hemin-induced erythroid differentiation of human erythroleukemia K562 cells

“…Moreover, strong inhibition of terminal differentiation by T3 has been reported in Epo responsive NFS-60 cells [33] and we previously showed that T3 suppresses activin-induced K562 differentiation [19]. Hematopoietic progenitor cells obtained from hyperthyroid patients exhibit increased proliferative potential of BFU-Es and upregulation of cell cycle markers, compared to those from healthy volunteers [34]. These studies suggest that T3 exerts classical augmentation, but also has a suppressive effect on erythropoiesis, especially at a high concentration.…”

Effect on Renal Function of Restoration of Euthyroidism in Hyperthyroid Cats with Iatrogenic Hypothyroidism

“…These findings suggest that iatrogenic hypothyroidism has a negative effect on hematopoietic function, resulting in a reduction in red cell mass, and a concurrent negative effect on cardiovascular function, that together might increase morbidity (and thus perhaps mortality) in cats with iatrogenic hypothyroidism. Human patients with hypothyroidism are reported to have a macrocytic hypochromic anemia, which is associated with a reduced proliferative potential of hematopoietic stem cells 11. It is possible that a similar pathophysiologic mechanism could account for the reduced PCV that was observed in hypothyroid cats in the present study; however, further studies would be required to confirm this.…”

Correlation Between Hypothyroidism and Iron Deficiency Anemia in Female Patients

“…[22] Meanwhile, hypothyroidism will case anemia due to affect blood cells. [23] In this study, the levels of ferritin and HB were recorded to low in female patients with hypothyroidism as compared to healthy controls. These results are agreed with other studies which revealed that iron deficiency may be associated with low levels of thyroid hormones.…”