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Erythropoietin is a glycoprotein. It acts on the bone marrow to increase the production of red blood cells. Stimuli such as bleeding or moving to high altitudes (where oxygen is scarcer) trigger the release of EPO.
People with failing kidneys can be kept alive by dialysis. But dialysis only cleanses the blood of wastes. Without a source of EPO, these patients suffer from anemia. Now, thanks to recombinant DNA technology, recombinant human EPO is available to treat these patients.
Some other uses for recombinant EPO:
Because EPO increases the hematocrit, it enables more oxygen to flow to the skeletal muscles. Some cyclists (and distance runners) have used recombinant EPO to enhance their performance. Although recombinant EPO has exactly the same sequence of amino acids as the natural hormone, the sugars attached by the cells used in the pharmaceutical industry differ from those attached by the cells of the human kidney. This difference can be detected by a test of the athlete's urine.
Another problem: since recombinant EPO became available, over two dozen young competitive cyclists have died unexpectedly (usually during the night). Perhaps an EPO-induced increase in their hematocrit — leading to a reduction in heart rate — is responsible.
Prolonged exposure to reduced oxygen levels (e.g., living at high altitude) leads to increased synthesis of EPO. In mice, and perhaps in humans, this effect is mediated by the skin. Mouse skin cells can detect low levels of oxygen ("hypoxia") and if this persists, blood flow to the kidneys diminishes leading to increased synthesis of EPO by them.
EPO is also synthesizedCalcitriol acts on
Calcitriol enters cells and, if they contain receptors for it (intestine cells do), it binds to them. The calcitriol receptors are zinc-finger transcription factors. The receptor-ligand complex bind to its response element, the DNA sequence:
5' AGGTCAnnnAGGTCA 3'This sequence of nucleotides (n can be any nucleotide) is found in the promoters of genes that are turned on by calcitriol. Once the hormone-receptor complex is bound to its response element, other transcription factors are recruited to the promoter and transcription of the gene(s) begins.
The most common causes are inadequate amounts of the vitamin in the diet or insufficient exposure to the sun.
However, some rare inherited cases turn out to be caused by inheriting two mutant genes for the kidney enzyme that converts 25[OH] vitamin D3 into calcitriol.
Other cases of inherited rickets (also very rare) are caused by inheriting two defective genes for the calcitriol receptor. Mutations that change the amino acids in one or another of the zinc fingers interfere with binding to the DNA of the response element.
One of the functions of the kidney is to monitor blood pressure and take corrective action if it should drop. The kidney does this by secreting the proteolytic enzyme renin.
Although called a vitamin, calciferol and its products fully qualify as hormones because they are
This hormone of 28 amino acids is released from stretched atria (hence the "A").
This hormone (29 amino acids) is released from the ventricles. (It was first discovered in brain tissue; hence the "B".)
The latter two effects reduce the reabsorption of water by the kidneys. So the volume of urine increases as does the amount of sodium excreted in it. The net effect of these actions is to reduce blood pressure by reducing the volume of blood in the circulatory system.
These effects give ANP and BNP their name (natrium = sodium; uresis = urinate).
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