title: 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.
  
  
  METHODS
  The influence of THs through TH receptors (TRalpha-1 and TRbeta-1) on haematopoiesis in patients with hypo- and hyperthyroidism was analysed.
  
  
  METHODS
  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.
  
  
  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 CD34(+)-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(+)-enriched HPCs and iii) the molecular mechanism by which THs influence haematopoiesis might provide a basis for designing novel therapeutic interventions in thyroid diseases.
authors.affiliation: Department of Physiology, Pomeranian Medical University, 72 Powstancow Wlkp Street, 70-111 Szczecin, Poland.
authors.forename: Milosz Piotr
authors.initials: MP
authors.lastname: Kawa
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Grymula
authors.forename: Edyta
authors.initials: E
authors.lastname: Paczkowska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Baskiewicz-Masiuk
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Dabkowska
authors.forename: Monika
authors.initials: M
authors.lastname: Koziolek
authors.forename: Maciej
authors.initials: M
authors.lastname: Tarnowski
authors.forename: Patrycja
authors.initials: P
authors.lastname: Kłos
authors.forename: Violetta
authors.initials: V
authors.lastname: Dziedziejko
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kucia
authors.forename: Anhelli
authors.initials: A
authors.lastname: Syrenicz
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Machalinski
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood* / Q000503:physiopathology; D007037:Hypothyroidism / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics* / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D012333:RNA, Messenger; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta