MECHANISM OF INCREASED SPLENIC ERYTHROPOIESIS IN MICE TREATED WITH ESTRADIOL BENZOATE

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 88  (5) , 700-706
Abstract
Pharmacological doses of estrogens induce osteosclerosis of the bone marrow, and depress colony-forming units (CFU''s) and platelet and leukocyte counts in mice. A compensatory increase in splenic erythropoiesis prevents a fall in the hematocrit. The mechanism of this compensation was investigated as follows. BDF1 female mice were injected s.c. 3 times weekly for 6 wk with 50 .mu.g of estradiol benzoate (EB) or sesame oil (SO). Subsequently the hematocrit, red cell mass (RCM) and 4 h percent of 59Fe uptake into the femurs and spleens were determined in groups of 5 mice for 4 consecutive days. The RCM and hematocrit were not significantly different in the 2 groups. The percent of 59Fe uptake into the femurs of EB-treated mice was < 30% of that in SO-treated mice and the percent of 59Fe uptake into the spleens of EB mice was more than 2 times that in SO mice. To ascertain whether the increase in splenic erythropoiesis resulted from an increase in the number of splenic erythropoietin-responsive cells (ERC), the 4 h percent 59Fe uptake into the spleen was determined in continuously hypertransfused EB and SO mice injected with erythropoietin (Ep). Whereas hypertransfusion depressed the splenic percent of 59Fe uptake in EB and SO mice equally, injection of Ep increased the percent of 59Fe uptake into the spleens of EB mice to > 2 times that of SO mice. Next, the plasma Ep level of mice injected with EB or SO for 2, 4, or 6 wk was determined after exposure of the animals to hypoxia. Ep titers were > 3 times higher in EB mice than in SO mice. At least 2 mechanisms act to cause the compensatory increase in splenic erythropoiesis after marrow suppression by EB: the Ep levels rise and the splenic ERC population increases. The latter is probably not due to the increased plasma Ep level because it also occurs in mice whose Ep production is suppressed by plethora.