Erythropoietin is now accepted as the hormone controlling red blood cell production. A radioimmunoassay has been developed in this laboratory using pure radioiodine labeled erythropoietin and an anti-erythropoietin-antiserum prepared in rabbits. This assay measures not only normal circulating levels, but also depressed levels seen following physiological conditions known to depress erythropoiesis, and increased hormone levels associated with stimuli known to increase erythropoiesis, such as bleeding, hypoxia or cobalt administration. This radioimmunoassay shows a significant correlation with the in vivo bioassay for erythropoietin. Using this method, polycythemias of primary origin are distinguishable from those of secondary origin. The clinical significance of this proposal is derived from the diagnostic value of a sensitive assay of blood levels of erythropoietin. Clinical work proposed in this study deals with erythropoietin responses in infants born to diabetic or hypertensive mothers. Fetal hypoxemia in high risk pregnancies can be diagnosed by measuring the hormone level in the amniotic fluid. In addition to human erythropoietin a variety of animal erythropoietins are measurable with this assay. Animal work proposed is concerned with the ontogeny of Ep producing tissues in the fetal rat. The role of this hormone in neonatal erythropoiesis will be investigated as well as the site(s) of production and concentrations in response to anemia and hypoxia as a function of age and sex. The effects of exogenous Ep will be investigated in neonatal rabbits in order to gain information on whether the newborn animal metabolizes Ep differently than the adult. These studies may be of future clinical value in treatment of the anemia in premature infants with recombinant erythropoietin. Other animal studies are concerned with the effect of other hormones on renal erythropoietin synthesis and release, and with extrarenal sources of erythropoietin in adult animals. The possible function of high Ep levels found in rodent salivary glands will be further pursued. The knowledge gained from these investigations will add significantly to our understanding of the biogenesis and hormonal control of erythropoietin and to the role of this hormone in normal and diseased states in humans.
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