Erythropoietin and the Regulation of Erythropoiesis by Sanford B. Krantz and Leon O. Jacobson (review)

BOOK REVIEW Erythropoietin and the Regulation ofErythropoiesis. By Sanford B. Krantz and Leon O. Jacobson. Chicago: University of Chicago Press, 1970. Pp. 330. $6.75. The polycythemia in men and animals living at high altitudes was long believed to represent a direct response ofthe bone marrow to low oxygen tensions. This hypothesis was effectively disposed of in 1950 by experiments with parabiotic rats. One was kept hypoxic, yet both members of the pair demonstrated increased red cell production. Only a hormone produced in the hypoxic animal and blood-borne to the fully oxygenated parabiotic mate could account for the findings. This experiment can be considered a paradigm in view ofthe fact that a scientific revolution relating to the hormonal control of erythropoiesis followed. This book, by two of the foremost investigators in the field, Krantz and Jacobson, presents the exciting story of this revolution. It started effectively in 1953—1955 and is continuing with increasing tempo at the present time. The hormone is erythropoietin. It is produced in the kidney and controls the differentiation ofthe erythropoietic cells of the marrow. Hypoxia is a principal stimulus to the production of the hormone. After fifteen years of intense study represented by over 1,000 primary references, the biochemistry and pathophysiology of the hormone are now well understood. The hormone is believed to be a glycoprotein with a molecular weight ofabout 65,000. It acts on certain primitive cells in the marrow to guide their differentiation down the track leading to the mature circulating red blood cell. The effect ofthe hormone on the differentiation ofthe primitive cells appears to be mediated by RNA synthesis, and through both its transcriptional and translational effects, the production ofhemoglobin is made possible. The key that opened the door to these discoveries was the development of bioassays for the hormone. At first crude and cumbersome, these procedures have reached the level where the effects ofthe hormone can be studied at the molecular level in marrow cells in vitro. The discovery oferythropoietin and elucidation ofits action appear to be offar-reaching significance in biology and medicine. A model is provided for the control ofcellular differentiation as well as a hope for precise bioengineering in the medical management of certain anemias due to inadequate erythropoietin stimulus to the bone marrow. The book, in spite of the technical nature of many aspects of the subject, is very readable. It should become the reference book in the field for the student oferythropoiesis. It will also be ofgreat value to the general biologist interested in the steady state, cellular kinetics, and tissue differentiation. K. M. Brinkhous, M.D. Department ofPathology University ofNorth Carolina, Chapel Hill 675 ...