International Journal of Cell Cloning, Vol 4, 139-166, Copyright © 1986 by AlphaMed Press
The mechanism of action of erythropoietin
JL Spivak
The proliferation and differentiation of committed erythroid progenitor
cells is regulated by the glycoprotein hormone erythropoietin.
Erythropoietin increases the number of developing erythroid precursors and
accelerates the release of reticulocytes from the marrow without markedly
altering the cell cycle length or number of mitotic divisions involved in
the differentiation process. Although the hormone has been purified,
molecularly cloned and sequenced, its secondary and tertiary structure and
active site have not been defined. Erythropoietin has both mitogenic and
differentiation functions, and whether an erythroid progenitor cell
responds to the hormone by proliferating or differentiating appears to
depend on its level of maturation. Erythroid progenitor cells are
responsive to a variety of growth and developmental agents but only
erythropoietin appears obligatory in vivo for terminal differentiation.
Erythropoietin interacts with its target cells through specific
high-affinity receptors and Ca2+ may be involved in the receptor-ligand
interaction. Ca2+ may also be involved in the induction of differentiation
by erythropoietin. An increase in RNA synthesis due to activation of
transcription is one of the earliest recognized effects of the hormone and
appears not to require protein or DNA synthesis but the initial sequence of
biochemical events triggered by erythropoietin is still undefined.
