Archives of Toxicology

, Volume 88, Issue 1, pp 137–144 | Cite as

Suppression of erythropoietin induction by diethylstilbestrol in rats

  • Hyogo Horiguchi
  • Etsuko Oguma
  • Takako Sakamoto
  • Katsuyuki Murata
  • Fujio Kayama
Organ Toxicity and Mechanisms


Diethylstilbestrol is an estrogenic endocrine disrupter that has diverse health effects in humans. Bisphenol A is another estrogen-like chemical with possible similar effects to diethylstilbestrol, which has been increasingly used for industry to lead to globally widespread human exposure to it. Hematopoiesis is another of their possible targets, since estrogen suppresses erythropoietin induction to induce anemia. The aim of this study was to clarify the effects of diethylstilbestrol and bisphenol A on erythropoietin induction in rats. We observed the effects of one-shot subcutaneous injection of diethylstilbestrol or bisphenol A on hypoxia-, bleeding-, and cobalt-stimulated erythropoietin induction within 24 h and the hematological outcomes after repeated subcutaneous injection of diethylstilbestrol three times a week for 1 month in rats. Diethylstilbestrol at 10–1,000 μg/kg suppressed stimulus-elevated levels of plasma erythropoietin and its renal mRNA induction. In contrast, bisphenol A at 1,000 μg/kg did not suppress plasma erythropoietin elevated by any stimuli. Repeated injection of diethylstilbestrol at 1,000 μg/kg to rats for 1 month induced an anemic trend due to decelerated erythropoiesis through the insufficient production of erythropoietin, mimicking the effects of estradiol. In conclusion, diethylstilbestrol has a suppressive effect on erythropoietin induction, leading to deceleration of erythropoiesis and the development of anemia.


Anemia Bisphenol A Diethylstilbestrol Estrogen Erythropoietin Rat 



This research was supported by research grants from CREST-JST and Grant-in-Aid for the Encouragement of Young Scientists (A) (no. 12770179) from the Ministry of Education, Science, and Culture of Japan. The authors gratefully acknowledge that this publication was subsidized by JKA through its promotion funds from KEIRIN RACE.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Hyogo Horiguchi
    • 1
    • 2
    • 3
  • Etsuko Oguma
    • 1
    • 2
    • 3
  • Takako Sakamoto
    • 2
  • Katsuyuki Murata
    • 1
  • Fujio Kayama
    • 2
    • 3
  1. 1.Department of Environmental Health Sciences, Graduate School of MedicineAkita UniversityAkitaJapan
  2. 2.Department of Environmental and Preventive Medicine, School of MedicineJichi Medical UniversityTochigiJapan
  3. 3.Core Research for Evolutional Science and Technology, Japan Science Technology Corporation (CREST-JST)SaitamaJapan

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