Regulation of Erythropoiesis XXII. Erythropoietin Production in the Newborn Animal

Abstract

Erythropoietin production was examined in the newborn rat. Even though there was significant anemia present during the early neonatal phase of life in the rat, erythropoietin could not be demonstrated in the plasma. Exposure to simulated levels of altitude of 23,000 feet for a period of 18 hr. resulted in the production of demonstrable levels of erythropoietin in the plasma. The amount of erythropoietic activity which could be demonstrated in the plasma of hypoxic animals increased with age from values of 0.76 units/ml. in the 1 day old animal to normal adult values of approximately 8 units/ml. by the thirtieth day of life. Bilateral nephrectomy prior to exposure to hypoxia in the 5 day old and 15 day old rat reduced the amount of erythropoietin to values of 50 per cent and 25 per cent of those observed in the intact hypoxic animal. By the thirtieth day of life, erythropoietin could no longer be demonstrated in anephric animals exposed to hypoxia. It is concluded that there is a gradual increase in the capacity of the rat to produce erythropoietin in response to an hypoxic stimulus, and that in significant measure during the early neonatal phase, erythropoietin production is accomplished by extrarenal sources.

The erythroid cells and haemoglobins of the chick embryo

“…Erythropoietin appears necessary for the production of recognizable erythroid cells in the adult mouse (Bleiberg, Liron & Feldman 1967;Curry, Trentin & Wolf 1967;Schooley 1967). However, the haematologic response of neonatal rodents, such as mice and rats, to anaemia, starvation, hypoxia, or nephrectomy (treatments which influence erythro poietin production in adult rodents) differs from that of adult animals subjected to similar treatment (Lucarelli et al 1968;Lucarelli & Butturini 1967;Carmena, Howard & Stohlman 1968;Stohlman 1970). During early neonatal life the response of the young rodents becomes progressively more similar to that of adult animals (Carmena et al 1968, Stohlman 1970.…”

“…However, the haematologic response of neonatal rodents, such as mice and rats, to anaemia, starvation, hypoxia, or nephrectomy (treatments which influence erythro poietin production in adult rodents) differs from that of adult animals subjected to similar treatment (Lucarelli et al 1968;Lucarelli & Butturini 1967;Carmena, Howard & Stohlman 1968;Stohlman 1970). During early neonatal life the response of the young rodents becomes progressively more similar to that of adult animals (Carmena et al 1968, Stohlman 1970. Similarly, the supression of erythroid colony formation in the spleens of lethally irradiated, plethoric mice injected with liver cell suspensions prepared from 12-to 19-day foetal mice was only partial (Bleiberg & Feldman 1969).…”

Erythropoiesis‐stimulating factor(s), erythropoiesis and erythrocyte 2,3‐diphospho‐glycerate in young rabbits with marked postnatal fall in haemoglobin

“…In adult animals the erythropoietic activity is not linked to the level of H b per se, but is mainly regulated through renal erythropoietin production, in response to changes in the 0, tension in 0,-sensing regions in the kidney (Fisher 1983). The 0,-dependent regulatory mechanism seems to be established already during fetal life (Finne 1968, Meberg 1980, H l g i & Kristiansen 1981, Thomaset al 1983, but partoftheerythropoietin production is extra-renal (Zanjani et al 1977, HHgl & Kristiansen 1981.…”

Hypoxia-inducible factors not only regulate but also are myeloid-cell treatment targets

“…14 Later, the liver was identified as an additional extrarenal EPO source. [15][16][17][18][19][20][21][22] Most clinical observations supported the importance of the kidneys for erythropoiesis with complete erythroblastopenia in anuric renal failure patients 23 and after nephrectomy, 24 and polycythemia in patients with renal pathologies, such as renal cysts, hypernephroma, or hydronephrosis. [25][26][27][28][29][30][31][32][33] In the 1970s, EPO was isolated from the urine of anemic patients [34][35][36] followed by cloning and recombinant expression a decade later.…”

“…The investigators observed that bilateral nephrectomy abrogated the erythropoietic effect of CoCl 2 in rats and rabbits 14 . Later, the liver was identified as an additional extrarenal EPO source 15–22 . Most clinical observations supported the importance of the kidneys for erythropoiesis with complete erythroblastopenia in anuric renal failure patients 23 and after nephrectomy, 24 and polycythemia in patients with renal pathologies, such as renal cysts, hypernephroma, or hydronephrosis 25–33 .…”