Journal of Glycobiology
Open Access

Mechanism of Erythropoietin (Glycoprotein Hormone) in Anemic Conditions

Linda Fabio Dewa^{* *}Correspondence: Linda Fabio Dewa, Center for Proteomics and Metabolomics, Leiden University, The Netherlands, Email:

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Description

Erythropoietin (EPO) is a glycoprotein hormone that plays a crucial role in the regulation of red blood cell production (erythropoiesis). EPO acts on the bone marrow, particularly on the erythroid progenitor cells, to stimulate their proliferation and differentiation into mature red blood cells. This process is essential for maintaining adequate oxygen-carrying capacity in the blood. EPO production is tightly regulated by oxygen levels in the body. When oxygen levels decrease (hypoxia), as in conditions like anemia or at high altitudes, the kidneys release more EPO to boost red blood cell production and enhance oxygen transport. Recombinant human erythropoietin has been developed and is used clinically to treat certain types of anemia, especially in conditions like chronic kidney disease and cancer- related anemia. It can help reduce the need for blood transfusions in these patients.

Types of erythropoietin

• Endogenous EPO is a natural erythropoietin produced by the body. The primary sources of endogenous EPO are the kidneys and, to a lesser extent, the liver. The production of endogenous EPO is regulated by oxygen levels in the blood.

• Darbepoetin alfa is a type of EPO with an extended half-life compared to traditional recombinant EPO. It is used in the treatment of anemia associated with chronic kidney disease and chemotherapy.

• Biosimilar versions of EPO have been developed, offering alternatives to the original recombinant human EPO. These biosimilars are designed to be highly similar to the reference product and have comparable efficacy and safety.

Mechanism of erythropoietin

The primary stimulus for EPO production is hypoxia, or low oxygen levels in the blood. Specialized cells in the kidneys, known as peritubular fibroblasts, are particularly sensitive to changes in oxygen concentration. In normoxic (normal oxygen) conditions, a protein called Hypoxia-Inducible Factor (HIF) is hydroxylated, leading to its degradation. In hypoxic conditions, the hydroxylation process is inhibited, leading to the stabilization of HIF. Stabilized HIF translocates to the nucleus of renal cells, where it binds to specific DNA sequences called Hypoxia- Response Elements (HREs) within the EPO gene. The binding of HIF to HREs initiates the transcription of the EPO gene, resulting in the formation of messenger RNA (mRNA) for EPO.

The mRNA leaves the nucleus and enters the cytoplasm, where it serves as a template for the synthesis of EPO through the process of translation. Once synthesized, EPO is released into the bloodstream from the kidneys and, to a lesser extent, the liver. In the bone marrow, EPO binds to specific receptors on the surface of erythroid progenitor cells, stimulating their proliferation and differentiation into mature red blood cells. The newly formed red blood cells are released into the bloodstream, increasing the overall oxygen-carrying capacity of the blood. This helps to restore oxygen homeostasis in response to the initial hypoxic stimulus.

Erythropoietin disease conditions

Chronic Kidney Disease (CKD): Reduced kidney function in chronic kidney disease often leads to lower production of erythropoietin. This can result in anemia due to insufficient stimulation of red blood cell production.

Cancer-related anemia: Some types of cancer, as well as cancer treatments such as chemotherapy, can lead to anemia. Recombinant erythropoietin is sometimes used in the treatment of anemia associated with cancer.

Myelodysplastic Syndromes (MDS): MDS are a group of disorders characterized by dysfunctional blood cell production in the bone marrow. Erythropoietin-stimulating agents may be used to address anemia in some MDS cases.

HIV/AIDS: Anemia can occur in individuals with HIV/AIDS, and erythropoietin-stimulating agents may be considered in the management of anemia in these patients.

Endocrine disorders: Certain endocrine disorders, such as hypothyroidism or adrenal insufficiency, may impact erythropoietin levels and contribute to anemia.

Hypoxia-induced conditions: Any condition or circumstance leading to chronic hypoxia (low oxygen levels) can stimulate the production of erythropoietin. This includes respiratory disorders such as Chronic Obstructive Pulmonary Disease (COPD) or high-altitude living.

EPO treatment

EPO treatment is often considered for individuals with anemia associated with chronic kidney disease, cancer chemotherapy, and certain other conditions where the production of endogenous EPO is insufficient. Blood tests are used to measure hemoglobin levels, and the dosage of EPO may be adjusted based on the patient's individual needs. The duration of EPO treatment varies depending on the underlying condition and the patient's response. In some cases, it may be a short-term intervention to address acute anemia, while in other cases, such as chronic kidney disease, it may be a long-term or ongoing treatment. Like any medication, EPO is associated with potential side effects. These can include hypertension (high blood pressure), clotting events, and, rarely, pure red cell aplasia. Healthcare providers carefully monitor patients for these complications. In certain situations, EPO treatment may be used in combination with other therapies, such as iron supplementation, to optimize its effectiveness.

Conclusion

It's important to note that the use of erythropoietin or erythropoietin-stimulating agents in medical treatments is typically done under the supervision of healthcare professionals and is based on careful assessment of the underlying condition. In sports or non-medical contexts, the use of erythropoietin for performance enhancement is considered unethical and is prohibited due to potential health risks and unfair advantages. Any use of erythropoietin for medical purposes should be discussed with a qualified healthcare provider.