Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1976 Jan;57(1):57–62. doi: 10.1172/JCI108269

Potentiation of erythropoiesis in vitro by dexamethasone.

D W Golde, N Bersch, M J Cline
PMCID: PMC436625  PMID: 173742

Abstract

The effect of dexamethasone on erythropoiesis was examined in vitro. Hematopoietic cells from 13-day mouse fetal livers were cultured for 48 h in the presence or absence of erythropoietin and erythroid colonies enumerated. Colony formation occurring in cultures containing no added erythropoietin was inhibited by the incorporation of antierythropoietin antibody, suggesting that these colonies formed in response to endogenous hepatic erythropoietin. Maximal colony formation was observed with 0.5 U/ml of sheep erythropoietin. Dexamethasone increased erythroid colony formation with peak stimulation at 10(-9) M. Dexamethasone potentiation was most marked in cultures containing less than maximally stimulating concentrations of erythropoietin. The cells required only a brief exposure to glucocorticosteroid to exhibit the augmented cloning capacity, and dexamethasone stimulation was inhibited by progesterone (10(-6) M). A comparable response to dexamethasone was observed in cultures of adult murine and human bone marrow erythroid progenitors, implying that the phenomenon is not peculiar to fetal cells and is not dependent on the presence of fetal hepatocytes. These data suggest that erythroid progenitor cells possess a glucocorticoid receptor mechanism that can modulate the response to erythropoietin in vitro.

Full text

PDF
57

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CARDINALI G., CARDINALI G., DECARO B. M., HANDLER A. H., ABOUL-ENEIN M. EFFECT OF HIGH DOSES OF CORTISONE ON BONE MARROW CELL PROLIFERATION IN THE SYRIAN HAMSTER. Cancer Res. 1964 Jul;24:969–972. [PubMed] [Google Scholar]
  2. Cantor L. N., Morris A. J., Marks P. A., Rifkind R. A. Purification of erythropoietin-responsive cells by immune hemolysis. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1337–1341. doi: 10.1073/pnas.69.6.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang S. C., Sikkema D., Goldwasser E. Evidence for an erythropoietin receptor protein on rat bone marrow cells. Biochem Biophys Res Commun. 1974 Mar 25;57(2):399–405. doi: 10.1016/0006-291x(74)90944-9. [DOI] [PubMed] [Google Scholar]
  4. DIAMOND L. K., ALLEN D. M., MAGILL F. B. Congenital (erythroid) hypoplastic anemia. A 25-year study. Am J Dis Child. 1961 Sep;102:403–415. doi: 10.1001/archpedi.1961.02080010405019. [DOI] [PubMed] [Google Scholar]
  5. Engel W., Frowein J. Glucocorticoids and hCG sensitivity of rat testicular Leydig cell. Nature. 1974 Sep 13;251(5471):146–148. doi: 10.1038/251146a0. [DOI] [PubMed] [Google Scholar]
  6. Fried W. The liver as a source of extrarenal erythropoietin production. Blood. 1972 Nov;40(5):671–677. [PubMed] [Google Scholar]
  7. Gordon A. S., Mirand E. A., Zanjani E. D. Mechanisms of prednisolone action in erythropoiesis. Endocrinology. 1967 Aug;81(2):363–368. doi: 10.1210/endo-81-2-363. [DOI] [PubMed] [Google Scholar]
  8. Gospodarowicz D. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth. Nature. 1974 May 10;249(453):123–127. doi: 10.1038/249123a0. [DOI] [PubMed] [Google Scholar]
  9. Gregory C. J., McCulloch E. A., Till J. E. Erythropoietic progenitors capable of colony formation in culture: state of differentiation. J Cell Physiol. 1973 Jun;81(3):411–420. doi: 10.1002/jcp.1040810313. [DOI] [PubMed] [Google Scholar]
  10. Horn Y., Price D. C. The effect of androgens on erythroid and granulocytic marrow recovery in the irradiated rat. Acta Haematol. 1972;48(5):300–306. doi: 10.1159/000208474. [DOI] [PubMed] [Google Scholar]
  11. Iscove N. N., Sieber F. Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture. Exp Hematol. 1975 Jan;3(1):32–43. [PubMed] [Google Scholar]
  12. Iscove N. N., Sieber F., Winterhalter K. H. Erythroid colony formation in cultures of mouse and human bone marrow: analysis of the requirement for erythropoietin by gel filtration and affinity chromatography on agarose-concanavalin A. J Cell Physiol. 1974 Apr;83(2):309–320. doi: 10.1002/jcp.1040830218. [DOI] [PubMed] [Google Scholar]
  13. Malgor L. A., Torales P. R., Klainer T. E., Barrios L., Blanc C. C. Effects of dexamethasone on bone marrow erythropoiesis. Horm Res. 1974;5(5):269–277. doi: 10.1159/000178640. [DOI] [PubMed] [Google Scholar]
  14. Meints R. H., Carver F. J. Triiodothyronine and hydrocortisone effects on Rana pipiens erythropoiesis. Gen Comp Endocrinol. 1973 Aug;21(1):9–15. doi: 10.1016/0016-6480(73)90151-2. [DOI] [PubMed] [Google Scholar]
  15. Metcalf D. Cortisone action on serum colony-stimulating factor and bone marrow in vitro colony-forming cells. Proc Soc Exp Biol Med. 1969 Oct;132(1):391–394. doi: 10.3181/00379727-132-34222. [DOI] [PubMed] [Google Scholar]
  16. Mizoguchi H., Levere R. D. Enhancement of heme and globin synthesis in cultured human marrow by certain 5 -H steroid metabolites. J Exp Med. 1971 Dec 1;134(6):1501–1512. doi: 10.1084/jem.134.6.1501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Peschle C., Sasso G. F., Mastroberardino G., Condorelli M. The mechanism of endocrine influences on erythropoiesis. J Lab Clin Med. 1971 Jul;78(1):20–29. [PubMed] [Google Scholar]
  18. Pospísil M., Zakopalová I., Netíková J. The effect of hydrocortisone pretreatment upon erythropoietic recovery after a single sublethal x-ray exposure of mice. Folia Biol (Praha) 1972;18(4):284–291. [PubMed] [Google Scholar]
  19. Rosenblum A. L., Carbone P. P. Androgenic hormones and human granulopoiesis in vitro. Blood. 1974 Mar;43(3):351–356. [PubMed] [Google Scholar]
  20. Rousseau G. G., Baxter J. D., Higgins S. J., Tomkins G. M. Steroid-induced nuclear binding of glucocorticoid receptors in intact hepatoma cells. J Mol Biol. 1973 Sep 25;79(3):539–554. doi: 10.1016/0022-2836(73)90405-1. [DOI] [PubMed] [Google Scholar]
  21. Rousseau G. G., Baxter J. D., Tomkins G. M. Glucocorticoid receptors: relations between steroid binding and biological effects. J Mol Biol. 1972 Jun 14;67(1):99–115. doi: 10.1016/0022-2836(72)90389-0. [DOI] [PubMed] [Google Scholar]
  22. Schooley J. C., Mahlmann L. J. Extrarenal erythropoietin production by the liver in the weanling rat. Proc Soc Exp Biol Med. 1974 Mar;145(3):1081–1083. doi: 10.3181/00379727-145-37957. [DOI] [PubMed] [Google Scholar]
  23. Shahidi N. T. Androgens and erythropoiesis. N Engl J Med. 1973 Jul 12;289(2):72–80. doi: 10.1056/NEJM197307122890205. [DOI] [PubMed] [Google Scholar]
  24. Stephenson J. R., Axelrad A. A., McLeod D. L., Shreeve M. M. Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1542–1546. doi: 10.1073/pnas.68.7.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Toohey J. I. Sulfhydryl dependence in primary explant hematopoietic cells. Inhibition of growth in vitro with vitamin B12 compounds. Proc Natl Acad Sci U S A. 1975 Jan;72(1):73–77. doi: 10.1073/pnas.72.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wardle D. F., Malpas J. S., Wrigley P. F. Bioassay of erythropoietin using foetal mouse liver cells. Br J Haematol. 1973 Jan;24(1):49–56. doi: 10.1111/j.1365-2141.1973.tb05726.x. [DOI] [PubMed] [Google Scholar]
  27. Zanjani E. D., Mann L. I., Burlington H., Gordon A. S., Wasserman L. R. Evidence for a physiologic role of erythropoietin in fetal erythropoiesis. Blood. 1974 Aug;44(2):285–290. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES