Hormones erythropoietin

Erythropoietin -hormonal stimulant of red blood cell production —erythrocytosis (with excessive dosage) -flushing... 

Wrighton, N.C., et al. Small peptides as potent mimetics of the protein hormone erythropoietin. Science 273 458-463, 1996. 

There are undifferentiated stem cells of the blood elements in the bone marrow that differentiate and mature into erythrocytes, (red blood cells), thrombocytes (platelets), and white blood cells (leukocytes and lymphocytes). The production of erythrocytes is regulated by a hormone, erythropoietin (see the section on kidney toxicity), that is synthetized and excreted by the kidney. An increase in the number of premature erythrocytes is an indication of stimulation of erythropoiesis, i.e., increased production of erythrocytes in anemia due to continuous bleeding. 

Cytokine receptors that couple to the JAK-STAT Pathway decode the signaling though hematopoietic cytokines (erythropoietin, thrombopoietin, colony-stimulating factors), prolactin, growth hormone, the a-, (3- and y- interferons, and a number of immunomodulatory interleukins [3], They form homodimetic or heterodimeric receptor complexes, which after ligandbinding recruit and activate isotypes of Janus kinases (JAKs). Activated JAKs in turn... 

Anemia may occur in patients with chronic renal failure as tlie result of the inability of the kidney to produce erythropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia Two examples of drug used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp). 

The availability of a cDNA for erythropoietin has made it possible to produce substantial amounts of this hormone for analysis and for therapeutic purposes previously the isolation of erythropoietin from human urine yielded very small amounts of the protein. The major use of recombinant erythropoietin has been in the treatment of a small number of anemic states, such as that due to renal failure. 

The progenitor cells of the kidney produce 90% of the hormone erythropoietin (EPO), which stimulates red blood cell (RBC) production. Reduction in nephron mass decreases renal production of EPO, which is the primary cause of anemia in patients with CKD. The development of anemia of CKD results in decreased oxygen delivery and utilization, leading to increased cardiac output and left ventricular hypertrophy (LVH), which increase the cardiovascular risk and mortality in patients with CKD. 

Erythropoietin A hormone primarily produced by the progenitor cells of the kidney that stimulates red blood cell production in the bone marrow. Lack of this hormone leads to anemia. 

Erythropoietin is a glycoprotein hormone that regulates the proliferation, differentiation, and maturation of erythroid cells. The EPO receptor is a member of the class 1 cytokine receptor superfamily. The crystal structure of an EPO-mimetic peptide and the extracellular portion of the... 

Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin is a peptide hormone that stimulates red blood cell production in bone marrow. Its primary source is the kidneys. Erythropoietin is secreted in response to renal hypoxia. Chronic renal disease may impair the secretion of erythropoietin, leading to development of anemia. The kidneys also produce enzymes. The enzyme renin is part of the renin-angiotensin-aldosterone system. As will be discussed, these substances play an important role in the regulation of plasma volume and therefore blood pressure. Other renal enzymes are needed for the conversion of vitamin D into its active form, 1,25-d i hyd ro xyv itamin D3, which is involved with calcium balance. 

Hormones and Related Substances—includes erythropoietin (EPO) and growth hormone... 

Figure 4.20 (b) those receptors which recruit cytosolic TK receptors for growth hormone, erythropoietin (EPO), Prolactin. Binding of hormone, for example leptin, causes dimerisation of the receptor and attachment of cytosolic TK which phosphorylate protein substrate(s)... 

Structure and physiology of the kidney glomerular filtration tubular activity selective reabsorption and secretion, often using specific carrier mechanisms carbonic anhydrase and acid-base balance. The kidney also produces, and is sensitive to, hormones actions of the hormones ADH, aldosterone and PTH the kidney as a secretory organ erythropoietin, the renin-angiotensin system vitamin D3. 

The other hormone of note synthesized by kidney is erythropoietin (EPO), a glycosylated peptide hormone (molecular weight approximately 50 000), which promotes red blood cell formation and is secreted in response to poor oxygen perfusion (hypoxia) of the kidney. This, along with the control of blood pressure via the RAA system illustrates the importance of the kidney in regulating aspects of the blood vascular system. Further details of EPO can be found in Chapter 5. 

There are many examples of ELIS As used for detecting host cell impurities in the literature. Pauly et al.12 developed an ELISA to detect impurities in erythropoietin that had a detection limit of around 0.05 ng/ml. SDS polyacrylamide gel and Western blot analysis were used to confirm the spectrum of proteins detected and to demonstrate the specificity of the antibody preparation. Anicetti et al.14 describe an assay for the detection of E. coli proteins in recombinant DNA-derived human growth hormone. Whitmire and Eaton15 report on an immuno-ligand assay for quantitation of process-specific E. coli host cell contaminant proteins in a recombinant bovine somatotropin. 

Erythropoiesis (A). Blood corpuscles develop from stem cells through several cell divisions. Hemoglobin is then synthesized and the cell nucleus is extruded. Erythropoiesis is stimulated by the hormone erythropoietin (a glycoprotein), which is released from the kidneys when renal O2 tension declines. 

In addition to their involvement in excretion and metabolism, the kidneys also have endocrine functions. They produce the hormones erythropoietin and calcitriol and play a decisive part in producing the hormone angiotensin II by releasing the enzyme renin. Renal prostaglandins (see p. 390) have a local effect on Na resorption. 

Erythropoietin is a peptide hormone that is formed predominantly by the kidneys, but also by the liver. Together with other factors known as colony-stimulating factors" (CSF see p.392), it regulates the differentiation of stem cells in the bone marrow. 

Erythropoietin release is stimulated by hypoxia (low PO2). Within hours, the hormone ensures that erythrocyte precursor cells in the bone marrow are converted to erythrocytes, so that their numbers in the blood increase. Renal damage leads to reduced erythropoietin release, which in turn results in anemia. Forms of anemia with renal causes can now be successfully treated using erythropoietin produced by genetic engineering techniques. The hormone is also administered to dialysis patients. Among athletes and sports professionals, there have been repeated cases of erythropoietin being misused for doping purposes. 

Certain medicines may not be imported under the personal importation provisions, including drugs of abuse, such as narcotics, amphetamines and psychotropic substances, and anabolic substances, androgenic steroids and treatments for alcohol and drug addiction. There are also controls over certain other medicines including erythropoietin, growth hormones and gonadotrophins. 

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