ERYTHROPOIETIN ERYTHROPOIETIN

By - Sahithi Sahithi

INTRODUCTION INTRODUCTION Erythropoietin is also called as Hemopoietin

or Erythrocyte Stimulating Factor

or Erythropoiesis Stimulating Agent.

HISTORYHISTORY

In 1906, Paul Carnot, a professor of medicine of Paris

with his assistant DeFlandre proposed that “Hormones

regulate the production of red blood cells”. . Eva Bonsdorff coined the name for the hemopoietic

substance as ‘ERYTHROPOIETIN’ERYTHROPOIETIN’. Lin in 1985 , isolated the erythropoietin gene of

human being from a genomic phage library. 1989 , US food and Drug Administration approved the

use of EPOGEN.

STRUCTURE

Erythropoietin is a Glycoprotein.

Protiens – 74%

carbohydrates – 26%

It contains 165 amino acid residues

with a molecular weight of 34,000.

Half life is 5hrs.

SOURCE In fetus & neonate, the major site of formation of

erythropoietin is in liver.

In adults, there are two sources which

involve in the production of

erythropoietin.

Renal source – 85%

Hepatic sources – 15%

ERYTHROPOIETIN RECEPTOR AND ERYTHROPOIETIN RECEPTOR AND MECHANISM OF ACTIONMECHANISM OF ACTIONErythropoietin ReceptorErythropoietin Receptor:- The receptor for erythropoietin is a linear protein with

a single transmembrane domain that is a member of the cytokine receptor superfamily.

Mechanism of action:-Mechanism of action:- Erythropoietin binds to the receptor on the target cells.

The receptor has tyrosine kinase activity and it activates a cascade of serine and threonine kinase, inhibiting apoptosis of red cells resulting in growth and development of target cells.

FUNCTIONS

Important effect of erythropoietin is to stimulate the

production of proerythroblasts from hematopoietic

stem cells in the bone marrow.

FUNCTIONS OTHER THAN HAEMOPOIESIS

Increase iron absorption. Vasoconstriction dependent hypertension. Angiogenesis . Proliferation of smooth muscle fibers. Epo can also effects the mood. It promotes haemoglobin synthesis by

increasing globin synthesis and potentiating δ amino levulinic acid synthetase.

Epo binds with EpoR receptors on red cells and induce jak2 signalling cascade.

FACTORS INFLUENCING FACTORS INFLUENCING ERYTHROPOIETIN PRODUCTIONERYTHROPOIETIN PRODUCTION

Factors increases erythropoietin secretions.Factors increases erythropoietin secretions.Hypoxia.Hormones.Nucleotides.

Factors Decreases Erythropoietin Secretions.Factors Decreases Erythropoietin Secretions.OestrogenAdenosine antagonist.

HYPOXIA HYPOXIA Hypoxia is a potent stimulator of Erythropoietin secretion from Kidney.

HypoxiaHypoxia HypoxiaHypoxia

ERYTHROPOIETINERYTHROPOIETIN

ERYTHROPOIESIS

(Haemopoetic Stem Cells In Bone Marrow)

Stimulates “Hypoxia inducible factors present in kidney”

HormonesHormones Androgens : specially “TESTOSTERONE”. They

increases the no. of stem cells in bone marrow,

stimulates the production of erythropoietin.

Thyroid Hormones: “ TH ” alternate the gene

expression and also stimulates erythropoietin by

increasing renal tissue hypoxia.

Nucleotides: cAMP , NAD and NADP increases Epo

secretion.

Products released after destruction of RBC after

120 days of life span are also stimulates Epo

secretion.

FACTORS DECREASES ERYTHROPOIETIN FACTORS DECREASES ERYTHROPOIETIN SECRETIONSSECRETIONS

Estrogen: decrease the erythropoietin

secretions by inhibiting stem cell response.

Adenosine antagonist.

INACTIVATION INACTIVATION

Principle site of inactivation of

erythropoietin is in liver.

RECOMBINANT ERYTHROPOIETIN

A recombinant erythropoietin which is produced

in animal cells for therapeutic use.

They are

1.Epoetin α.

Epogen

Procit

Aransep …Etc.

USES OF RE COMBINAT EPO

To treat patients with anaemia Chronic renal disease. Crohn’s disease. Cancer patients under chemotherapy and

radiation.

APPLIED ASPECTS

Erythropoietin is also used to stimulate RBC

production in individuals who are banking a supply of

their own blood in preparation for autologous

transfusions during elective surgery.

Blood doping : Due increase muscle ability by

increase

the delivery of oxygen, Epo is misused by athletes.