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Physiology of the kidney (7/7): Erythropoetin, Endothelins and Vitamin D

• Anatomy of the kidney (1/7): Gross anatomy
• Anatomy of the kidney (2/7): Histology of the glomerulus and nephron
• Anatomy of the kidney (3/7): Histology of renal tubules
• Anatomy of the kidney (4/7): Physiology of the glomerular filtration rate
• Anatomy of the kidney (5/7): Physiology of the tubular reabsorption
• Anatomy of the kidney (6/7): Physiology of the renin-angiotensin-aldosterone system
• Anatomy of the kidney (7/7): Physiology of erythropoetin, endothelins and vitamin D

Review literature: (Benninghoff, 1993) (Jelkmann, 2004) (Schmidt and Thews, 1995).

Erythropoetin (EPO)

Erythropoetin, also spelled Erythropoietin, is a growth hormone that controls erythropoieses (formation of red blood cells). Target cells of Erythropoetin are the red cell precursors in the bone marrow (colony forming unit-erythroid, CFU-E). The duration of the erythrocyte development from precursors to the reticulocyte takes 7 days and includes 4–6 cell divisions.

Molecular Structure of Erythropoetin

Erythropoetin is a glycoprotein, the protein part consists of 165 amino acids and mediates the cytokine function. The carbohydrate part of 40% protects the hormone from proteolysis in vivo. Overall, Erythropoetin has a mass of 30 kDa. Minor differences in the carbohydrate part between physiological and recombinant Erythropoetin enables doping controls using electrophoresis.

Production Location of Erythropoetin

During fetal hematopoiesis, erythropoetin is formed in the liver. After birth, most of the erythropoetin is produced in interstitial peritubular kidney cells (fibroblasts) in the renal cortex. In small amounts, Erythropoetin is also produced in the CNS and has functions in the neuroprotection.

Concentration of Erythropoetin

The concentration of Erythropoetin is expressed in Units (U). 1 U Erythropoetin corresponds to the erythropoietic activity of 5 g cobalt chloride in animal experiments. The normal concentration in blood is 5-25 U/l, during hypoxia or anemia, the concentration increases up to 10 000 U/l.

Control of Erythropoetin

The physiological stimulus for the production and secretion of Erythropoetin is hypoxemia and anemia. The signal transduction cascade for the activation of Erythropoetin is complex and involves HIF 1–3 (hypoxia inducible factors) and HRE (hypoxia response elements) sequences of the DNA. After the release, Erythropoetin binds to the Erythropoetin receptor of the target cells CFU-E, which is a tyrosine kinase receptor. The signaling prevents apoptosis of the target cell in the bone marrow.

Endothelins

Endothelins are a group of peptide hormones, which are activated via a cascade system like the renin-angiotensin-aldosterone system (RAAS). Functions of endothelins are potent vasoconstriction, retention of sodium and raising the blood pressure. Furthermore, endothelins have pathophysiological significance in kidney diseases, heart failure, arteriosclerosis and pulmonary hypertension.

Further Endocrine Functions of the Kidney

Activation of Vitamin D

Hydroxylation of 25-hydroxyvitamin D₃ to 1,25-hydroxyvitamin D₃ (cholecalciferol = calcitriol).

References

  Deutsche Version: Physiologie der Nieren: Erythropoetin.