ERITROPOETYN (Greek erythros red + poietikos creating, making; a synonym an eritropoezsti-muliruyushchy factor) — the hormone of the gli-koproteinovy nature stimulating proliferation and a differentiation of an eritropoetinchuvstvitelny cell in morphologically recognizable erythroblasts.
For the first time E. it was found by Carnot and Deflandr (P. Carnot, S. Def-landre) in 1906 (see Hematinic principles). In 1974. Commission on the biochemical nomenclature of the International union of theoretical and applied chemistry and International biochemical union E. it was included in the list of the peptide hormones received in pure form.
In an experiment it is proved that E. is permanent fiziol. the regulator erythrocyto-poeza (see the Hemopoiesis, regulation of a hemopoiesis). Contents E. reflects a condition of a marrowy hemopoiesis in a stage of unrecognizable predecessors of erythrocytes therefore its research in biol. liquids opens ample opportunities of an in-depth study normal erythrocyto-poeza and its disturbances. Definition E. it is applied as the test to studying of eritropoetinoobrazuyu-Russian cabbage soup of system of an organism at patol. conditions of kidneys, a functional condition of an erythrocytopoiesis at anemias, differential diagnosis of a polycythemia and secondary hyperglobulias with the obscure etiology, in the presence of the hidden tumoral processes, for control of a condition of an erythrocytopoiesis at treatment gematol. diseases.
AA. it is purely received from a blood plasma of sheep with the anemia caused by administration of phenylhydrazine and wet patients with aplastic anemia. Electrophoretic mobility E. same as at a2-globulin, the isoelectric point is at pH 4,5 — 5,0, and a pier. the weight (weight) is equal to 41 000 — 46 Ltd companies. It is supposed that hormone exists in the form of monomer, a dimeasure or a complex of both forms. The hormones emitted from a blood plasma of sheep and urine of the person are similar on structure. They contain 65 — 76% of protein and carbohydrates, in structure to-rykh there is a glucose, mannose, sialine to - that, a galactose and a glycosamine. A proteinaceous part has a one-chain structure, contains apprx. 340 amino acids, at the same time the prevailing quantity is presented by acid amino acids, to-rye together with sialic acid (see) cause a low isoelectric point of E. Sialovaya to - that defines biol. stability of hormone as its «bessialovy» form communicates hepatocytes and, like other glycoproteins, is quickly brought out of circulation.
It is considered that the factor stimulating education E. in an organism, undervoltage of oxygen in fabrics is. Synthesis of hormone happens generally in kidneys what increase in its content in blood in response to the decrease in oxygenation of kidneys caused by a hypoxia (see) testifies to. At patol. processes in kidneys low contents E is noted. in blood, not corresponding to degree of anemia. Assume that in kidneys the inactive predecessor E is formed. — the renal stimulating erythrocyto-poez factor (eritrogenin, pre-erythropoetin), to-ry is activated at contact with a plasma factor (a2-globulin), Along with it the active form of hormone can be also formed in kidneys. Localization of formation of hormone is finally not found out. Hormone was emitted from brain and cortical substance of a kidney. Education E. it is connected with function of nephron in general. Synthesis E. or his predecessor it is carried out by activation cyclic 3', 5 '-AMF and a cyclic guanozinmonofosfat with participation of renal prostaglandins (see).
Consider that normal the liver does not participate in education E., however also the wedge, data testimonial of the fact that during removal of a kidney or disturbance of its endocrine function the liver assumes a role of eritropoe-tinsinteziruyushchy body are received experimental.
The main target cell for E. morphologically unrecognizable erythroidal predecessors are that was shown in an experiment on mice with an oppressed erythrocytopoiesis. Dynamics of changes of erythroblasts in marrow and a spleen of mice, and also registration of effect in size of inclusion 69Fe in erythrocytes or on number of the reticulocytes which appeared in blood in 48 — 72 hours after single introduction E., point to existence of group of the cells standing among a differentiation is higher, than a proerythroblast (see the Hemopoiesis). This cell was called an eritropoe-tinchuvstvitelny cell.
By means of methods of cultivation of cells three types of erythroidal predecessors are allocated: bursoobrazuyushchy units — BOE1E, BOE2E and colony-forming erythroidal unit — KOEe (see Cultures of cells and fabrics). Influence E. it is carried out at a stage of BOE2E and KOEe. There are data that E. activates proliferation and maturing of the erythroblasts which are in marrow during introduction E., and also stimulates maturing of reticulocytes and their exit in a blood channel.
For biol. methods of definition of activity E. use mice with an oppressed erythrocytopoiesis. In the beginning cause a hyperglobulia by contents in animals them on
8 — 20 hours a day in a pressure chamber with a pressure of 0,4 — 0,5 atm during 15 — 24 days or by means of introduction of 70 — 80% of suspension of the washed homologous erythrocytes. Against the background of the coming oppression of an erythrocytopoiesis an animal enter the studied material into the post-hypoxemic or posttransfusion period and then on number of the reticulocytes which appeared in blood or on inclusion of radioactive iron in erythrocytes judge erythropoietic activity of hormone. The size of erythropoietic activity is determined in milliyedinitsa (honey) by comparison of erythropoietic activity of the studied hormone and referens-drug E., to-ry previously titrate according to the International standard of erythropoetin. There are three International standards: standard «A» (E. it is received from a blood plasma of sheep with the anemia caused by administration of phenylhydrazine), the standard I and the standard II (E. it is allocated respectively from urine of patients with aplastic anemia and with a helminthic invasion). Sensitivity biol. methods of definition of activity E. makes 20 — 100 honey/ml.
From in the vitro methods apply a method of definition E. in culture of an embryonal liver of mice and radio-immuno a logical method. Chuvst
the vitelnost of these methods is higher, than sensitivity biol. methods. Due to the lack of the unified standard E. high extent of cleaning in a wedge, practice in the vitro method for determination of content E. in biol. liquids (blood, urine) do not apply. It is shown that E. makes 0,0003% of proteins of a blood plasma even at anemia.
Normal concentration E. in blood of the person and animals makes 10 — 50 honey/ml. At various states (e.g., hypoxias), and also at nek-ry gematol. diseases contents E. in blood increases by 50 — 100 times, at the same time the amount of the formed hormone, as a rule, depends on expressiveness of anemia. At high content E. in blood it comes to light usually and in urine, but by 2 — 5 times of smaller concentration.
Bibliography: Kinetic aspects haemo -
a poeza, under the editorship of G. I. Kozints and E. D. Goldberg, Tomsk, 1982; The Normal hemopoiesis and its regulation, under the editorship of
N. A. Fedorov, page 341, M., 1976; Physiology of system of blood, Physiology of an erythrogenesis, under the editorship of V. N. Chernigovsky, etc., page 118, L., 1979; Dunn C. D. a. Lange R. D. Erythropoietin titers in normal human serum, an appraisal of assay techniques, Exp. Hematol., v. 8, p. 231, 1980; E s p a d a J., Langton A. A. a. Dorado M. Human erythropoietin, Sta-dies on purity and partial characterization, Biochim. biophys. Acta (Amst.), v. 285, p. 427, 1972; Fisher J. W. Extrare-nal erythropoietin production, J. Lab. clin. Med., v. 93, p. 695, 1979; Goldwas-s e r E. Erythropoietin, Blut, v. 33, p. 135, 1976; Kidney hormones, ed. by J. W. Fisher, v. 2, L. a. lake, 1977.
V. I. Gudim.