Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1973 Sep;52(9):2278–2282. doi: 10.1172/JCI107415

Effective Erythropoiesis Induced by 5β-Pregnane-3β-Hydroxy-20-One in Squirrel Monkeys

Emmanuel C Besa 1, Dov Gorshein 1, William A Hait 1, Frank H Gardner 1
PMCID: PMC333031  PMID: 4199416

Abstract

The erythropoietic effect of 5β-pregnane-3β-hydroxy-20-one, a naturally occurring steroid metabolite of progesterone, was evaluated in the squirrel monkey by ferrokinetic studies. red cell survival, and blood volume measurements. The intramuscular administration of this steroid in pharmacologic doses shortened the 59Fe plasma clearance and increased the plasma iron turnover, thereby indicating an increase in erythropoiesis. A normal 59Fe red cell uptake was observed, and the bone marrow maturation time was not altered. Red cell survival was the same in the treated and control groups. After five weekly injections of the steroid, the monkeys increased their red cell mass by 57%. A significant increase in white blood cells and a slight elevation of platelet counts in the treated monkeys also suggest a possible direct stimulation of hemopoietic stem cells by the steroid metabolite.

These observations indicate that some steroid metabolites can stimulate an early increase in iron turnover (within 48 h) that is not secondary to hemolysis. The increased red cell mass indicates effective erythropoiesis in primates.

Full text

PDF
2279

Selected References

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

  1. Bottomley S. S., Smithee G. A. Effect of erythropoietin on bone marrow delta-aminolevulinic acid synthetase and heme synthetase. J Lab Clin Med. 1969 Sep;74(3):445–452. [PubMed] [Google Scholar]
  2. Byron J. W. Comparison of the action of 3 H-thymidine and hydroxyurea on testosterone-treated hemopoietic stem cells. Blood. 1972 Aug;40(2):198–203. [PubMed] [Google Scholar]
  3. CARTWRIGHT G. E., ATHENS J. W., WINTROBE M. M. THE KINETICS OF GRANULOPOIESIS IN NORMAL MAN. Blood. 1964 Dec;24:780–803. [PubMed] [Google Scholar]
  4. Fisher J. W., Samuels A. I., Malgor L. A. Androgens and erythropoiesis. Isr J Med Sci. 1971 Jul-Aug;7(7):892–900. [PubMed] [Google Scholar]
  5. Fried W., Gurney C. W. The erythropoietic-stimulating effects of androgens. Ann N Y Acad Sci. 1968 Mar 29;149(1):356–365. doi: 10.1111/j.1749-6632.1968.tb15169.x. [DOI] [PubMed] [Google Scholar]
  6. Gordon A. S., Zanjani E. D., Levere R. D., Kappas A. Stimulation of mammalian erythropoiesis by 5beta-H steroid metabolites. Proc Natl Acad Sci U S A. 1970 Apr;65(4):919–924. doi: 10.1073/pnas.65.4.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gorshein D., Gardner F. H. Erythropoietic activity of steroid metabolites in mice. Proc Natl Acad Sci U S A. 1970 Mar;65(3):564–568. doi: 10.1073/pnas.65.3.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Granick S., Kappas A. Steroid induction of porphyrin synthesis in liver cell culture. I. Structural basis and possible physiological role in the control of heme formation. J Biol Chem. 1967 Oct 25;242(20):4587–4593. [PubMed] [Google Scholar]
  9. Hait W. N., Gorshein D., Jepson J. H., Besa E. C., Gardner F. H. 19-Nortestosterone decanoate induced erythropoiesis in the actinomycin-D-treated hyperoxic mouse. Biochem Biophys Res Commun. 1972 Apr 28;47(2):426–431. doi: 10.1016/0006-291x(72)90731-0. [DOI] [PubMed] [Google Scholar]
  10. KAPPAS A., PALMER R. H. Selected aspects of steroid pharmacology. Pharmacol Rev. 1963 Mar;15:123–167. [PubMed] [Google Scholar]
  11. Kappas A., Levere R. D., Granick S. The regulation of porphyrin and heme synthesis. Semin Hematol. 1968 Oct;5(4):323–334. [PubMed] [Google Scholar]
  12. Kretchmar A. L., McDonald T. P., Lange R. D. Mode of action of erythropoietin in polycythemic mice. I. Response in mice treated with 5-fluorouracil. J Lab Clin Med. 1970 Jan;75(1):74–82. [PubMed] [Google Scholar]
  13. Levere R. D., Gordon A. S., Zanjani E. D., Kappas A. Stimulation of mammalian erythropoiesis by metabolites of steroid hormones. Trans Assoc Am Physicians. 1970;83:150–158. [PubMed] [Google Scholar]
  14. Levere R. D., Kappas A., Granick S. Stimulation of hemoglobin synthesis in chick blastoderms by certain 5beta androstane and 5beta pregnane steroids. Proc Natl Acad Sci U S A. 1967 Sep;58(3):985–990. doi: 10.1073/pnas.58.3.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Naets J. P., Wittek M. The mechanism of action of androgens on erythropoiesis. Ann N Y Acad Sci. 1968 Mar 29;149(1):366–376. doi: 10.1111/j.1749-6632.1968.tb15170.x. [DOI] [PubMed] [Google Scholar]
  17. Necheles T. F., Rai U. S. Studies on the control of hemoglobin synthesis: the in vitro stimulating effect of a 5-beta-H steroid metabolite on heme formation in human bone marrow cells. Blood. 1969 Sep;34(3):380–384. [PubMed] [Google Scholar]
  18. Reisner E. H., Jr Tissue culture of bone marrow. II. Effect of steroid hormones on hematopoiesis in vitro. Blood. 1966 Apr;27(4):460–469. [PubMed] [Google Scholar]
  19. Schooley J. C., Mahlmann L. J. Stimulation of erythropoiesis in the plethoric mouse by cyclic-AMP and its inhibition by antierythropoietin. Proc Soc Exp Biol Med. 1971 Sep;137(4):1289–1292. doi: 10.3181/00379727-137-35774. [DOI] [PubMed] [Google Scholar]
  20. Wilson J. D., Gloyna R. E. The intranuclear metabolism of testosterone in the accessory organs of reproduction. Recent Prog Horm Res. 1970;26:309–336. doi: 10.1016/b978-0-12-571126-5.50012-1. [DOI] [PubMed] [Google Scholar]

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

RESOURCES