Pharmacological Reviews, Vol 24, 459-508, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

Erythropoietin: Pharmacology, Biogenesis and Control of Production

¹ Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana

The purpose of this review has been to describe the pharmacological actions of erythropoietin and its role in the control of erythropoiesis. It includes: a historical introduction on the discovery of the humoral control of erythropoiesis; techniques used for the assay and standardization of erythropoietin; purification and physicochemical characterization of erythropoietin; renal and extrarenal sites of production of erythropoietin; the biogenesis of erythropoietin as it pertains to the renal erythropoietic factor (erythrogenin); and a schematic model for the renal control of erythropoietin production. Pharmacological agents included in this review which are known to increase erythropoietin production are androgens, pituitary ACTH (through an action on the release of glucocorticoids from the adrenal), angiotensin, norepinephrine, 5-hydroxytryptamine (5-HT), vasopressin, prostaglandins, dibutyryl cyclic 3’, 5’-AMP and cobalt. The pharmacological agents which depress erythropoietin production are the diuretic drugs, such as mercurials, triamterene, benzydroflumethiazide, as well as chlorambudil, thio-TEPA, actinomycin D, and ionizing radiation. Other areas in the review include: the nervous system and carotid body influences on erythropoiesis; physiological and pathological inhibitors of erythropoietin and erythropoiesis; the mechanisms and sites of action of erythropoietin on the erythron; and clinical anemias and polycythemias associated with erythropoietin secretion. The recent reports on the complete isolation, purification and characterization of erythropoietin offer hope that sufficient amounts of this glycoprotein-hormone will be available in the near future for the treatment of some of the erythropoietin deficiency anemias.

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