1. EPO stimulates erythropoiesis by:
Hypoxic conditions
Kidney Haem ‘Sensor’
EPO stimulates erythropoiesis by:
*increasing the number of committed cells capable of differentiating into erythrocytes;
*accelerating the rate of differentiation of such precursors;
*increasing the rate of haemoglobin synthesis in developing cells.
Haem Group in Deoxygenated conformation
Change in receptor configuration (intracellular domain)
Initiation of cell signalling cascade
Transcription factor now ‘activated’ and moves in to nucleus
Increase in RBCs number
Improved oxygenation (non hypoxic conditions)
Transcription factor docks on to specific response element in EPO gene promotor; activates EPO gene expression
Kidney Haem ‘Sensor’
Haem Group in oxygenated conformation
EPO mRNA transcribed
EPO Protein translated & secreted
Revert to normal receptor configuration
EPO travels to bone marrow (CFU-Es display EPO receptors per cell)
Reduction in EPO production