Studies on hormonal induction of embryonic erythropoiesis

Hunter, Jennifer A (1968) Studies on hormonal induction of embryonic erythropoiesis. PhD thesis, University of Glasgow.

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It has been established that the hormone, erythropoietin, is concerned in the control of normal adult erythropoiesis in mammals; it is known to act by stimulating maturation of progenitor cells. The part played by erythropoietin during foetal life in not clear; its mode of action on sensitive cells is also uncertain. The hormone may be assayed in vitro by neorurin the incorporation of 59Po into protein-bound ham by erythroid sell cultures. The erythroid activity and response to erythropoietin of cells from rat yolk sac, fcetal liver and foetal spleen were investigated; similar studies were carried out on rabbit foetal liver cells. The pattern of in vivo activity and sensitivity to erythropoietin observed during gestation suggested that, in both species, foetal erythropoiesis was controlled, in part, by erythropoietin; it was concluded that erythropoietin, probably of foetal origin, controlled red cell production except during yolk sac erythropoiesie. In many mammals the foetus produces haemoglobin distinct from the adult haemoglobin. Using starch gel electrophoresis the nature of the haemoglobins in circulating cells during gestation of mouse and rabbit foetuses was determined. Two haemoglobins were found in the blood of young rabbit footless; three were found in young mouse foetuses. In both species these disappeared during gestation and were replaced by a single adult haemoglobin. The site of production of the different haemoglobins was determined by starch gel electro-phoresis of 59Fe-labelled haemoglobin synthesised by erythroid cells in vitro. Only foetal haemoglobins were made by mouse yolk sac cells while only adult haemoglobin was made by foetal liver cells. Erythropoietin, to which only foetal liver cells were sensitive, stimulated only adult haemoglobin synthesis; it did not appear to affect haemoglobin synthesis directly, in circulating cells. Two haemoglobins were found in the blood of young rat foetuses; three others appeared during the early stages of foetal liver erythropoiesis. After birth, the amount of one of the components first present decreased to very lom levels in adult animals. The relative rates of synthesis of the haemoglobins were characteristic of the stage of gestation and remained the same during much, if not all, of cell maturation. It was found that erythropoietin treatment of feetal or adult erythroid cells had only a quantitative effect on haemoglobin synthesis; it did not alter the relative amounts of each haemoglobin present. As in mouse, it appeared to have no direct effect on haemoglobin synthesis by circulating cells. The effects of inhibitors, colchicine, FUdR, aotinomycin D and puromycin, on the response to erythropoietin of mouse foetal liver cells indicated that syntheses of DNA, RNA and protein, but not cell division, were essential for erythropoietin induced haemoglobin synthesis. Further studies indicated that cells usually divided after erythropoietin treatment but that this wan not mandatory for haemoglobin synthesis. The technique was altered to measure synthesis of DNA, RNA and total protein, as well as haem synthesis after erythropoietin treatment. These studies, including the effect of inhibitors upon the response, suggested that the first detectable result of erythropoietin treatment was mRNA synthesis; this permitted protein synthesis which was essential for DNA synthesis. These events occurred very quickly and DNA synthesis doubled within 1 hr. of crythropcietin treatment. Afterwards, cell maturation, including haemoglobin synthesis, could proceed. The time-course of the response suggested that erythropoietin might stimulate maturing cells, capable of DNA synthesis, as well as progenitor cells; the responding cells, whatever their nature, appeared to be sensitive to erythropoietin during the G1 period of their cycle. These results were discussed in relation to in vitro studies on other differentiating cells.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Developmental biology, Endocrinology
Date of Award: 1968
Depositing User: Enlighten Team
Unique ID: glathesis:1968-73799
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56

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