The regulatory role of the adrenergic agonists phenylephrine and isoproterenol on fetal hemoglobin expression and erythroid differentiation

Endocrinology. 2013 Dec;154(12):4640-9. doi: 10.1210/en.2013-1535. Epub 2013 Sep 30.


It has been reported that various endocrine hormones exert prominent effects on erythropoiesis. We conducted experiments to identify the mechanisms involved in the regulatory functions of adrenergic signaling on erythroid differentiation and the expression of hemoglobin genes. The reactivation of fetal hemoglobin (HbF) expression is also an important therapeutic option in patients with hemoglobin disorders. We determined that the adrenergic agonists phenylephrine (PE) and isoproterenol (ISO) can induce the production of β-hemoglobin embryonic 1 (hbbe1) mRNA and protein in adult zebrafish erythrocytes. Elevated levels of HbF mRNA and protein were also observed in human K562 cells after the adrenergic agonist treatments. In addition, elevated levels of histone acetylation were observed in both the PE- and the ISO-treated K562 cells. Additionally, our data further indicate that the induction effects of the adrenergic agonists on HbF synthesis and erythroid differentiation in K562 cells are mainly mediated by the p38 MAPK/cAMP response element binding pathway. In summary, the present study identifies the role of the adrenergic agonists PE and ISO on p38 MAPK and ERK signaling for the stimulation of HbF production and erythroid differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Line
  • Erythroid Cells / cytology*
  • Fetal Hemoglobin / genetics
  • Fetal Hemoglobin / metabolism*
  • Gene Expression Regulation
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Isoproterenol / pharmacology*
  • Leukemia, Erythroblastic, Acute / metabolism
  • MAP Kinase Signaling System
  • Phenylephrine / pharmacology*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Zebrafish
  • beta-Globins / genetics
  • beta-Globins / metabolism
  • gamma-Globins / genetics
  • gamma-Globins / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Histones
  • RNA, Messenger
  • beta-Globins
  • gamma-Globins
  • Phenylephrine
  • Fetal Hemoglobin
  • p38 Mitogen-Activated Protein Kinases
  • Isoproterenol