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Erythropoietin

Erythropoietin Abstract Erythropoietin is a polypeptide hormone that is apparently the primary regulator of erythropoiesis. This article reviews some of the current concepts regarding the site of erythropoietin (Ep) production, the mechanism by which it stimulates erythropoiesis, the assay systems available for measuring plasma and urinary Ep levels, and its role in the pathogenesis of anemias. Finally, some speculations on its future role in therapy for some anemias are included. References 1. Helmer OH: Purification, standardization and assay of renin and angiotensin , in Fisher JW (ed): Kidney Hormones . New York, Academic Press Inc, 1971, pp 59-76. 2. Jacobson LO, et al: Role of the kidney in erythropoiesis. Nature 179:633-634,1957.Crossref 3. Fraser DR, Kodicek E: Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature 228:764-765, 1970.Crossref 4. Lee JB, et al: The identification of prostaglandins E2, F2, and A2 from rabbit kidney medulla. Biochem J 105:1251-1260, 1967. 5. Bert P: Sur la richesse en hemoglobine du sang de animaux vivant sur les hauts. C R Acad Sci 94:805-806, 1882. 6. Carnot P, Deflandre C: Sur 1 'activite' hemapoietique des differents organes au cours de la regeneration du sang. C R Acad Sci 143:432-434, 1906. 7. Reissman KR: Studies on the mechanism of erythropoietic stimulation in parabiotic rats during hypoxia. Blood 5:372-380, 1950. 8. Erslev AJ: Humoral regulation of red cell production. Blood 8:349-357, 1953. 9. Stohlman F Jr, Rath CE, Rose JC: Evidence of a humoral regulation of erythropoiesis: Studies on a patient with polycythemia secondary to regional hypoxia. Blood 9:721-733, 1954. 10. Krantz SB, Jacobson LO: Erythropoietin and the regulation of erythropoiesis . Chicago, The University of Chicago Press, 1970. 11. Fisher JW: Erythropoietin: pharmacology, biogenesis, and control of production. Pharmacol Rev 24:459-508, 1972. 12. Gordon AS (ed): Red cell production , in Regulation of Hematopoiesis . New York, Appleton-Century-Crofts, 1970, vol 1, pp 1765. 13. Traunicek T, Neuwirt J (eds): The Regulation of Erythropoiesis Hemoglobin Synthesis . Prague, Karlova University, 1971. 14. Hodgson G, Toha J: The erythropoietic effects of urine and plasma in repeatedly bled rabbits. Blood 9:299-309, 1954. 15. Gordon AS, et al: A plasma extract with erythropoietic activity. Proc Soc Exp Biol Med 86:255-258, 1954.Crossref 16. Plzak LF, et al: Demonstration of stimulation of erythropoiesis by plasma from anemic rats using Fe59. J Lab Clin Med 46:671-678, 1955. 17. Gordon AS, et al: Erythropoietic action of a plasma filtrate in hypophysectomized rats. Proc Soc Exp Biol Med 89:246-248, 1955.Crossref 18. Fried W, et al: Erythropoiesis: II. Assay of erythropoietin in hypophysectomized rats. Proc Soc Exp Biol Med 92:203-207, 1956.Crossref 19. Fried W, et al: Studies on erythropoiesis: III. Factors controlling erythropoietin production. Proc Soc Exp Biol Med 94:237-241, 1957.Crossref 20. Gurney CW, Wackman N, Filmanowicz E: Studies on erythropoiesis: XVII. Some quantitative aspects of the erythropoietic response to erythropoietin. Blood 17:531-546, 1961. 21. Cotes PM, Bangham DR: Bioassay of erythropoietin in mice made plethoric by exposure to air at reduced pressure. Nature 191:1065-1067, 1961.Crossref 22. Gordon AS, Weintraub AH: Assay of the erythropoietic stimulating factor (ESF) , in Jacobson LO, Doyle M (eds): Erythropoiesis . New York, Grune & Stratton Inc, 1962, pp 1-16. 23. Degowin RL, Hofstra D, Gurney CW: The mouse with hypoxia induced erythremia, an erythropoietin bioassay animal. J Lab Clin Med 60:846-852, 1962. 24. Lange RD, Simmons ML, Dibelius NR: Polycythemic mice produced by hypoxia in silicone rubber membrane enclosures: A new technique. Proc Soc Exp Biol Med 122:761-764, 1966.Crossref 25. Fogh JA: A sensitive erythropoietin assay on mice exposed to CO-hypoxia. Scand J Clin Lab Invest 18:33-44, 1966.Crossref 26. Fried W, Gurney CW: Use of mild plethora to demonstrate an erythropoietic effect of small doses of androgens. Proc Soc Exp Biol Med 120:519-521, 1965.Crossref 27. Fogh J: The increased dose-response of ESF and ESF stimulation. Ann NY Acad Sci 149:217-224, 1968.Crossref 28. Cotes PM, Baugham DR: The international reference preparation of erythropoietin. Bull WHO 35:751-760, 1966. 29. Ito K, Reissman KR: Quantitative and qualitative aspects of steady state erythropoiesis induced in protein starved rats by long-term erythropoietin injection. Blood 27:343-351, 1966. 30. Adamson JW, et al: Erythropoietin excretion in normal man. Blood 28:354-364, 1966. 31. Alexanian R: Urinary excretion of erythropoietin in normal men and women. Blood 28:344-353, 1966. 32. Van Dyke DC, Nohr ML, Lawrence JH: Erythropoietin in the urine of normal and erythropoietically abnormal human beings. Blood 28:535-543, 1966. 33. Marver D, Gurney CW: Renal erythropoietin excretion as a function of acid-base balance. Ann NY Acad Sci 149:510-515, 1968.Crossref 34. Krantz S, Gallien-Lartigue BO, Goldwasser E: The effect of erythropoietin upon heme synthesis by marrow cells in vitro. J Biol Chem 238:4085-4090, 1963. 35. Lange RD, McDonald TP, Jordan T: Antisera to erythropoietin: Partial characterization of two different antibodies. J Lab Clin Med 73:78-90, 1969. 36. Fisher JW, Thompson JF, Espada J: Radioimmunoassay for human urinary erythropoietin. Isr J Med Sci 7:783-789,1971. 37. Jacobson LO, et al: Studies on erythropoiesis: VII. The role of the kidneys in the production of erythropoietin. Trans Assoc Am Physicians 70:305-317, 1957. 38. Naets JP: Erythropoiesis in nephrectomized dogs. Nature 181:1134-1135, 1958.Crossref 39. Kuratowska Z, Lewartowski B, Michalak E: Studies on the production of erythropoietin by isolated perfused organs. Blood 18:527-534, 1961. 40. Reissman KR, Nomura T: Erythropoietin formation in isolated kidneys and liver , in Jacobson LO, Doyle M (eds): Erythropoiesis . New York, Grune & Stratton Inc, 1962, pp 71-77. 41. Fisher JW, Birdwell BJ: The production of erythropoietic factor by the in situ perfused kidney. Acta Haematol 26:224-232, 1961.Crossref 42. Gurney CW, Goldwasser E, Pan C: Studies on erythropoiesis: IV. Erythropoietin in human plasma. J Lab Clin Med 50:534-540, 1957. 43. Gallagher NI, et al: Evaluation of plasma erythropoietic-stimulating factors in anemic uremic patients. Blood 14:662-667, 1959. 44. Gordon AS, et al: Attempts to identify the site of production of circulating erythropoietin. Proc Soc Exp Biol Med 92:598-602, 1956.Crossref 45. Kuratowska Z, Lewartowski B, Lipinski B: Chemical and biologic properties of an erythropoietic generating substance obtained from perfusates of isolated anoxic kidneys. J Lab Clin Med 64:226-237, 1964. 46. Kuratowska Z: The renal mechanism of the formation and inactivation of erythropoietin. Ann NY Acad Sci 149:128-134, 1968.Crossref 47. Contrera JF, et al: Extraction of erythropoietin from the kidneys of hypoxic phenylhydrazine treated rats. Blood 25:809-816, 1965. 48. Contrera JF, Gordon AS, Weintraub AH: Extraction of an erythropoietin producing factor from a particulate fraction of rat kidney. Blood 28:330-343, 1966. 49. Zanjani ED, et al: The renal erythropoietic factor (REF): III. Enzymatic role in erythropoietin production. Proc Soc Exp Biol Med 125:505-508, 1967.Crossref 50. Katz R, et al: Studies on the site of production of erythropoietin. Ann NY Acad Sci 149:120-127, 1968.Crossref 51. Gordon AS, Zanjani ED, Zalusky R: A possible mechanism of the erythrocytosis associated with hepatocellular carcinoma in man. Blood 35:151-157, 1970. 52. Malgor LA, Fisher JW: Effects of testosterone on erythropoietin production in the isolated perfused kidney. Am J Physiol 218:1732-1736, 1970. 53. Erslev AJ, Kazal LA: Renal erythropoietic factor: Lack of effect on hypertransfused mice. Blood 34:222-229, 1969. 54. Erslev AJ, Kazal LA, Miller OP: The action and neutralization of a renal lipid inhibitor of erythropoietin. Proc Soc Exp Biol Med 138:1025-1029, 1971.Crossref 55. Fisher JW, Taylor G, Porteous DD: Localization of erythropoietin in glomeruli of sheep kidney by fluorescent antibody technique. Nature 205:611-613, 1965.Crossref 56. Busuttil RW, Roh BL, Fisher JW: The cytological localization of erythropoietin in the human kidney using the fluorescent antibody technique. Proc Soc Exp Biol Med 137:327-330, 1971.Crossref 57. Osnes S: An erythropoietic factor produced in the kidney. Br Med J 2:1387-1390, 1958.Crossref 58. Gallagher NI, McCarthy JM, Lange RD: Erythropoietin production in uremic rabbits. J Lab Clin Med 57:281-289, 1961. 59. Erslev AJ: Erythropoietin function in uremic rabbits. Arch Intern Med 101:407-412, 1958.Crossref 60. Mirand AE, Prentice TC: Presence of plasma erythropoietin in hypoxic rats with or without kidneys and/or spleen. Proc Soc Exp Biol Med 96:49-51, 1957.Crossref 61. Nathan DG, Schupak E, Stohlman F: Erythropoiesis in anephric man. J Clin Invest 43:2158-2164, 1964.Crossref 62. Naets JP, Wittek M: Presence of erythropoietin in the plasma of one anephric patient. Blood 31:249-251, 1968. 63. Mirand EA, et al: Extrarenal production of erythropoietin in man. Acta Haematol 39:359-365, 1968.Crossref 64. Fried W, et al: Studies on extrarenal erythropoietin. J Lab Clin Med 73:244-248, 1969. 65. Carmena AO, Howard D, Stohlman F: Regulation of erythropoietin: XXII. Production in the newborn animal. Blood 32:376-382, 1968. 66. Wang F, Fried W: Renal and extrarenal erythropoietin production in male and female rats of various ages. J Lab Clin Med 79:181-186, 1972. 67. Fried W: The liver as a source of extrarenal erythropoietin. Blood 40:671-677, 1972. 68. Jacobson LO, et al: Studies of erythropoietin: The hormone regulating red cell production. Ann NY Acad Sci 77:551-559, 1959.Crossref 69. Kilbridge TM, Fried W, Heller P: The mechanism by which plethora suppresses erythropoiesis. Blood 33:104-113, 1969. 70. Necas E, Neuwirt J: Feedback regulation by red cell mass of the sensitivity of the erythropoietin producing organ to hypoxia. Blood 36:754-763, 1970. 71. Stohlman F, Brecher G: Humoral regulation of erythropoiesis: V. Relationship of plasma erythropoietin level to bone marrow activity. Proc Soc Exp Biol Med 100:40-43, 1959.Crossref 72. Hammond DA, Ishikama A, Keighly G: The relationship between erythropoietin and severity of anemia in hypoplastic and hemolytic states , in Jacobson LO, Doyle M (eds): Erythropoiesis . New York, Grune & Stratton Inc, 1962, pp 351-358. 73. Finne PH: On the correspondence between red cell production and plasma erythropoietin level. Scand J Clin Lab Invest 17:135-141, 1965.Crossref 74. Sanchez Medal L, Labardini J: Hemolysis and erythropoiesis: III. The effect of hemolysis and hemolysates on erythropoiesis. Ann NY Acad Sci 149:377-382, 1968.Crossref 75. Erslev A: The effect of hemolysates on red cell production and erythropoietin release. J Lab Clin Med 78:1-7, 1971. 76. Fried W, Rishpon Myerstein N, Gurney CW: The effect of testosterone on erythropoiesis of WWv mice. J Lab Clin Med 70:813-819, 1967. 77. Prentice TC, Mirand EA: Effect of acute liver damage plus hypoxia on plasma erythropoietin content. Proc Soc Exp Biol Med 95:231-234, 1957.Crossref 78. Reference deleted. 79. Alpen EL: The metabolic fate of erythropoietin , in Jacobson LO, Doyle M (eds): Erythropoiesis . New York, Grune & Stratton Inc, 1962, pp 135-139. 80. Keighly G: The metabolic fate of plasma erythropoietin , in Jacobson LO, Doyle M (eds): Erythropoiesis . New York, Grune & Stratton Inc, 1962, pp 106-110. 81. Kukral J, et al: The role of the liver in erythropoietin metabolism. Surg Forum 19:348, 1968. 82. Naets JP, Wittek M: Effect of erythroid hyperplasia on the utilization of erythropoietin. Nature 206:726-727, 1965.Crossref 83. Fried W, Johnson C, Heller P: Observations on regulation of erythropoiesis during prolonged periods of hypoxia. Blood 36:607-616, 1970. 84. Levy H, Levison U, Schade AL: The effect of cobalt on the activity of certain enzymes in homogenates of rat tissue. Arch Biochem 27:34-40, 1950. 85. Fisher JW, Samuels AI, Langston JW: Effects of angiotensin and renal artery constriction on erythropoietin production. J Pharmacol Exp Ther 157:618-625, 1967. 86. Zivny J, Neuwirt J, Borova J: The effect of aldosterone on erythropoietin production and erythropoiesis. J Lab Clin Med 80:217-223, 1972. 87. Evans ES, Rosenberg LL, Simpson ME: Erythropoietic response to calorigenic hormones. Endocrinology 68:517-532, 1961.Crossref 88. Fruhman GJ, Gordon AS: Effects of growth hormone and cortisol on hemopoiesis. Acta Haematol 15:249-262, 1956.Crossref 89. Jepson JH, Lowenstein L: Effect of prolactin on erythropoiesis in the mouse. Blood 24:726-738, 1964. 90. Schooley JC, Mahlmann LJ: Stimulation of erythropoiesis in plethoric mice by prostaglandins and its inhibition by anti-erythropoietin. Proc Soc Exp Biol Med 138:523-524, 1971.Crossref 91. Schooley JC, Mahlmann LJ: Stimulation of erythropoiesis in plethoric mice by cyclic AMP and its inhibition by anti-erythropoietin. Proc Soc Exp Biol Med 137:1289-1291, 1971.Crossref 92. Fried W, Gurney CW: The erythropoietic response to testosterone in male and female mice. J Lab Clin Med 67:420-426, 1966. 93. Mirand EC, Gordon AS: Mechanism of estrogen action in erythropoiesis. Endocrinology 78:325-332, 1966.Crossref 94. Giger K: Wirkung von Actinomycin-D auf die Erythropoietin Bildung während Hypoxie bei der Ratte. Klin Wochenschr 46:42-44, 1968.Crossref 95. Cooper GW, Zanjani ED, Gordon AS: Effect of steroid hormones on the production of the renal erythropoietic factor and erythropoietin. Fed Proc 27:383, 1968. 96. Dukes PP, Goldwasser E: Inhibition of erythropoiesis by estrogens. Endocrinology 69:21-34, 1961.Crossref 97. Jepson JH, Lowenstein L: Inhibition of the stem cell action of erythropoietin by estradiol. Proc Soc Exp Biol Med 123:457-460, 1966.Crossref 98. Miller ME, et al: pH effect on erythropoietin response to hypoxia, abstracted. Blood 40:966, 1972. 99. Faura J, Fried W, Gurney CW: The effects of CO2 on erythropoiesis , Ann NY Acad Sci 149:456-461, 1968.Crossref 100. Blacher LJ: On the influence of sexual hormones upon the number of erythrocytes and percentage quantity of hemoglobin in fowl. Biol Gen 2:435-440, 1926. 101. Steinglass P, Gordon AS, Charipper HA: Effect of castration and sex hormones on blood of the rat. Proc Soc Exp Biol Med 48:169-177, 1941.Crossref 102. Fried W, DeGowin R, Gurney CW: Erythropoietic effect of testosterone in the polycythemic mouse. Proc Soc Exp Biol Med 117:839-842, 1964.Crossref 103. Mirand EA, Gordon AS, Wenig J: Mechanism of testosterone action on erythropoiesis. Nature 206:270-272, 1965.Crossref 104. Mirand EA, et al: Effects of testosterone on renal hemodynamics and erythropoietin release in dogs. Invest Urol 4:203-207, 1966. 105. McCullogh EP, Jones R: Effect of androgens on the blood count of men. J Clin Endocrinol Metab 2:243-251, 1942.Crossref 106. Fried W, Gurney CW: Erythropoietic effect of plasma from mice receiving testosterone. Nature 206:1160-1161, 1965.Crossref 107. Rishpon Myerstein N, et al: The effect of testosterone on erythropoietin levels in anemic patients. Blood 31:453-460, 1968. 108. Alexanian R, Vaugh WH, Ruchelman MW: Erythropoietin excretion in man following androgens. J Lab Clin Med 70:777-785, 1967. 109. Fried W, Gurney CW: The erythropoietic stimulating effects of androgens. Ann NY Acad Sci 149:356-364, 1968.Crossref 110. Alexanian R: Erythropoietin and erythropoiesis in anemic man following androgens. Blood 33:564-572, 1969. 111. Fried W, Kilbridge T: Effect of testosterone and cobalt on erythropoietin production in anephric rats. J Lab Clin Med 74:623-629, 1969. 112. Mirand EA, et al: Erythropoietin activity in anephric allotransplanted, unilaterally nephrectomized and intact man. J Lab Clin Med 73:121-128, 1969. 113. Shaldon S, et al: Testosterone therapy of anemia in maintenance dialysis. Br Med J 3:212-215, 1971.Crossref 114. Schooley JC: Inhibition of erythropoietic stimulation by testosterone in polycythemic mice receiving anti-erythropoietin. Proc Soc Exp Biol Med 122:402-403, 1966.Crossref 115. Fried W, et al: Studies on the erythropoietin stimulating factor in the plasma of mice after receiving testosterone. J Lab Clin Med 68:947-951, 1966. 116. Gorsheim D, Gardner FH: Erythropoietic activity of steroid metabolites in mice. Proc Natl Acad Sci USA 65:564-568, 1970.Crossref 117. Gordon As, et al: Stimulation of mammalian erythropoiesis by 5 β-H steroid metabolites. Proc Natl Acad Sci USA 65:919-924, 1970.Crossref 118. Necheles TF, Rai US: Studies on the control of hemoglobin synthesis: The in vitro effect of 5 beta H steroid metabolites on hematopoiesis in vitro. Blood 34:380-384, 1969. 119. Levere RD, Kappas A, Granick S: Stimulation of hemoglobin synthesis in chick blastoderm by certain 5 β pregnane steroids. Proc Natl Acad Sci USA 58:985-990, 1967.Crossref 120. Besa EC, et al: Effective erythropoiesis by steroid metabolites in primates, abstracted. Blood 40:967, 1972. 121. Samuels AI, Fisher JW: Erythropoietic effects of 5α and β steroids. Fed Proc 30:203, 1971. 122. Byron JW: Comparison of the action of H3-thymidine and hydroxyurea on testosterone-treated hemopoietic stem cells. Blood 40:198-203, 1972. 123. Fried W, Knospe WH, Trobaugh FE Jr: Effect of testosterone on hematopoietic stem cells. Exp Haematol 21:38, 1971. 124. Schooley JC, et al: A summary of some studies on erythropoiesis using anti-erythropoietin immune serum. Ann NY Acad Sci 149:266-280, 1968.Crossref 125. Gurney CW, Pan C: Studies on erythropoiesis: IX. Mechanism of decreased erthropoiesis in experimental polycythemia. Proc Soc Exp Biol Med 98:789-793, 1959.Crossref 126. Alpen EL, Cranmore D: Cellular kinetics and iron utilization in bone marrow as observed by Fe59 radioautography. Ann NY Acad Sci 77:753-762, 1959.Crossref 127. Wolf NS, Trentin JJ: Hemopoietic colony studies: V. Effect of hemopoietic organ stroma on differentiation of plurpotential stem cells. J Exp Med 127:205, 1968.Crossref 128. Bruce WR, McCulloch EA: The effect of erythropoietic stimulation on hemopoietic colony forming cells of mice. Blood 23:216-232, 1964. 129. O'Grady LF, Lewis JP: Proliferation of erythroid committed cells in the absence of erythropoietin. J Lab Clin Med 76:445-450, 1970. 130. Reissman KR, Samorapoompichit S: Effect of erythropoietin on proliferation of erythroid stem cells in the absence of transplantable colony forming units. Blood 36:287-296, 1970. 131. Stephenson JR, Axelrad AH: Separation of erythropoietic sensitive cells from hemopoietic colony forming of mouse fetal liver by unit gravity sedimentation. Blood 37:417-430, 1971. 132. Hodgson G: Effect of vinblastine and 4 amino N10 methyl pteroly glutamic acid on the erythropoietin responsive cell. Proc Soc Exp Biol Med 125:1206-1209,1967.Crossref 133. Becker AJ, et al: The effect of differing demands for blood cell production on DNA synthesis by hemopoietic colony forming cells of mice. Blood 26:296-309, 1965. 134. Gross M, Goldwasser E: On the mechanism of erythropoietin induced differentiation: V. Characterization of the ribonucleic acid formed as a result of erythropoietin action. Biochemistry 8:1795-1805, 1969.Crossref 135. Bottomley SS, Smithee AG: Effect of erythropoietin on Δ-aminolevulinic acid synthetase and heme synthetase. J Lab Clin Med 74:445-452, 1969. 136. Powsner ER, Berman L: Effect of erythropoietin on DNA synthesis by erythroblasts in vivo. Blood 30:189-197, 1968. 137. Terada M, et al: Globin in RNA activity in erythroid cell precursors and the response to erythropoietin , in Abstracts From the American Society of Hematology: 15th Annual Meeting . 1972, p 36. 138. Morse BS, et al: The relationship of erythropoietin effectiveness to the generative cycle of the erythroid precursor cell. Blood 35:761-774, 1970. 139. Stohlman F Jr: Humoral regulation of erythropoiesis: XIV. A model for abnormal erythropoiesis in thalassemia. Ann NY Acad Sci 119:578-585, 1964.Crossref 140. Gordon AS, et al: Reticulocyte and leukocyte release from isolated perfused rat legs and femurs , in Jacobson LO, Doyle M (eds): Erythropoiesis . New York, Grune & Stratton Inc, 1962, pp 321-327. 141. Dukes PP, et al: Erythropoietin: A complex with different in vivo and vitro activities. J Lab Clin Med 76:439-444, 1970. 142. Borsook HA, et al: Polycythemic response in normal adult rats to a non-protein plasma extract from anemic rabbits. Blood 9:734-742, 1954. 143. Slaunwhite WR, Mirand EA, Prentice TC: Probable polypeptide nature of erythropoietin. Proc Soc Exp Biol Med 96:616-619, 1957.Crossref 144. Rambach WA, Alt HL, Cooper JAD: The mode of action and nature of a heat stable plasma erythropoietic factor. Blood 12:1101-1113, 1957. 145. Lowy PH, Keighley G, Borsook H: Inactivation of erythropoietin by neuraminidase and by mild substitution reactions. Nature 185:102-103, 1960.Crossref 146. Schooley JC, Garcia JF: The destruction by neuriminidase of the biological activity of erythropoietin when completed by antierythropoietin. Proc Soc Exp Biol Med 138:66-69, 1971.Crossref 147. Goldwasser E: Biochemical control of erythroid cell development , in Moury A, Nosona AA (eds): Current Topics In Developmental Biology . New York, Academic Press Inc, 1966, pp 173-211. 148. Espada J, Gutnitsky A: Purification of human urinary erythropoietin. Acta Physiol Lat Am 20:122-129, 1970. 149. Goldwasser E, Kung CKH: Purification of erythropoietin. Proc Natl Acad Sci USA 68:697-698, 1971.Crossref 150. Ward HP, Kurnick JE, Pisarczyk GJ: Serum level of erythropoietin in anemias associated with chronic infection, malignancy, and primary hematopoietic disease. J Clin Invest 50:332-335, 1971.Crossref 151. Kilbridge T, Fried W: Response of mice with a decreased number of hematopoietic stem cells to erythropoietin. J Lab Clin Med 72:85-92, 1968. 152. Shahidi NT, Diamond LK: Testosterone-induced remission in aplastic anemia. Am J Dis Child 98:293-301, 1959. 153. Gardner FH, Pringle JC: Androgens and erythropoiesis: II. Treatment of myeloid metaplasia. N Engl J Med 246:103-111, 1961.Crossref 154. Sanchez Medal L: The hemopoietic action of androstanes. Prog Hematol 7:111-141, 1971. 155. Lawrence JH: The treatment of chronic leukemias. Med Clin North Am 38:525-540, 1954. 156. DeGowin RL, et al: Erythropoiesis and erythropoietin in patients with chronic renal failure treated with hemodialysis and testosterone. Ann Intern Med 72:913-918, 1970.Crossref 157. Richardson JR, Weinstein MB: Erythropoietic response of dialyzed patients to testosterone administration. Ann Intern Med 73:403-407, 1970.Crossref 158. Shaldon S, et al: The use of testosterone in bilaterally nephrectomized dialysis patients. Trans Am Soc Artif Intern Organs 17:104-109, 1971. 159. Eschbach JW, et al: Erythropoiesis in patients with renal failure undergoing chronic dialysis. N Engl J Med 276:653-660, 1967.Crossref 160. Adamson JW: The erythropoietin hematocrit relationship in normal and polycythemic man: Implications of marrow regulation. Blood 32:597-608, 1968. 161. Krantz SB: Response of polycythemia vera marrow to erythropoietin in vitro. J Lab Clin Med 71:999-1012, 1968. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

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Abstract

Abstract Erythropoietin is a polypeptide hormone that is apparently the primary regulator of erythropoiesis. This article reviews some of the current concepts regarding the site of erythropoietin (Ep) production, the mechanism by which it stimulates erythropoiesis, the assay systems available for measuring plasma and urinary Ep levels, and its role in the pathogenesis of anemias. Finally, some speculations on its future role in therapy for some anemias are included. References 1. Helmer OH: Purification, standardization and assay of renin and angiotensin , in Fisher JW (ed): Kidney Hormones . New York, Academic Press Inc, 1971, pp 59-76. 2. Jacobson LO, et al: Role of the kidney in erythropoiesis. Nature 179:633-634,1957.Crossref 3. Fraser DR, Kodicek E: Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature 228:764-765, 1970.Crossref 4. Lee JB, et al: The identification of prostaglandins E2, F2, and A2 from rabbit kidney medulla. Biochem J 105:1251-1260, 1967. 5. Bert P: Sur la richesse en hemoglobine du sang de animaux vivant sur les hauts. C R Acad Sci 94:805-806, 1882. 6. Carnot P, Deflandre C: Sur 1 'activite' hemapoietique des differents organes au cours de la regeneration du sang. C R Acad Sci 143:432-434, 1906. 7. Reissman KR: Studies on the mechanism of erythropoietic stimulation in parabiotic rats during hypoxia. Blood 5:372-380, 1950. 8. Erslev AJ: Humoral regulation of red cell production. Blood 8:349-357, 1953. 9. Stohlman F Jr, Rath CE, Rose JC: Evidence of a humoral regulation of erythropoiesis: Studies on a patient with polycythemia secondary to regional hypoxia. Blood 9:721-733, 1954. 10. Krantz SB, Jacobson LO: Erythropoietin and the regulation of erythropoiesis . Chicago, The University of Chicago Press, 1970. 11. Fisher JW: Erythropoietin: pharmacology, biogenesis, and control of production. Pharmacol Rev 24:459-508, 1972. 12. Gordon AS (ed): Red cell production , in Regulation of Hematopoiesis . New York, Appleton-Century-Crofts, 1970, vol 1, pp 1765. 13. Traunicek T, Neuwirt J (eds): The Regulation of Erythropoiesis Hemoglobin Synthesis . Prague, Karlova University, 1971. 14. Hodgson G, Toha J: The erythropoietic effects of urine and plasma in repeatedly bled rabbits. Blood 9:299-309, 1954. 15. Gordon AS, et al: A plasma extract with erythropoietic activity. Proc Soc Exp Biol Med 86:255-258, 1954.Crossref 16. Plzak LF, et al: Demonstration of stimulation of erythropoiesis by plasma from anemic rats using Fe59. J Lab Clin Med 46:671-678, 1955. 17. Gordon AS, et al: Erythropoietic action of a plasma filtrate in hypophysectomized rats. Proc Soc Exp Biol Med 89:246-248, 1955.Crossref 18. Fried W, et al: Erythropoiesis: II. Assay of erythropoietin in hypophysectomized rats. Proc Soc Exp Biol Med 92:203-207, 1956.Crossref 19. Fried W, et al: Studies on erythropoiesis: III. Factors controlling erythropoietin production. Proc Soc Exp Biol Med 94:237-241, 1957.Crossref 20. Gurney CW, Wackman N, Filmanowicz E: Studies on erythropoiesis: XVII. Some quantitative aspects of the erythropoietic response to erythropoietin. Blood 17:531-546, 1961. 21. Cotes PM, Bangham DR: Bioassay of erythropoietin in mice made plethoric by exposure to air at reduced pressure. Nature 191:1065-1067, 1961.Crossref 22. Gordon AS, Weintraub AH: Assay of the erythropoietic stimulating factor (ESF) , in Jacobson LO, Doyle M (eds): Erythropoiesis . New York, Grune & Stratton Inc, 1962, pp 1-16. 23. Degowin RL, Hofstra D, Gurney CW: The mouse with hypoxia induced erythremia, an erythropoietin bioassay animal. J Lab Clin Med 60:846-852, 1962. 24. Lange RD, Simmons ML, Dibelius NR: Polycythemic mice produced by hypoxia in silicone rubber membrane enclosures: A new technique. Proc Soc Exp Biol Med 122:761-764, 1966.Crossref 25. 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Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jun 1, 1973

References