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. 1970 Apr;65(4):919–924. doi: 10.1073/pnas.65.4.919

Stimulation of Mammalian Erythropoiesis by 5β-H Steroid Metabolites*

Albert S Gordon 1,2,3, Esmail D Zanjani 1,2,3, Richard D Levere 1,2,3, Attallah Kappas 1,2,3
PMCID: PMC283004  PMID: 5266162

Abstract

The effects of a number of steroid compounds on erythropoiesis in normal and polycythemic mice were examined. Of the steroids that stimulated erythropoiesis, the hormone testosterone and certain 5β-H C19 and C21 nonhormonal metabolites were the most effective. Anti-erythropoietin abolished the erythropoiesis-stimulating effects of testosterone but not those exerted by the 5β-H steroid, 11-ketopregnanolone. Similarly, testosterone but not 11-ketopregnanolone evoked the production of erythropoiesis-stimulating factor in rats. It is concluded that two mechanisms underlie the stimulating actions of steroids on erythropoiesis; one through the production of erythropoietin and the second involving a more direct influence on the blood-forming tissues. The 5β-H steroid metabolites are postulated to act on erythropoiesis via the latter mechanism.

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Selected References

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

  1. Alexanian R. Erythropoietin and erythropoiesis in anemic man following androgens. Blood. 1969 Apr;33(4):564–572. [PubMed] [Google Scholar]
  2. Alexanian R., Vaughn W. K., Ruchelman M. W. Erythropoietin excretion in man following androgens. J Lab Clin Med. 1967 Nov;70(5):777–785. [PubMed] [Google Scholar]
  3. 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]
  4. Fried W., Gurney C. W. Erythropoietic effect of plasma from mice receiving testosterone. Nature. 1965 Jun 12;206(989):1160–1161. doi: 10.1038/2061160a0. [DOI] [PubMed] [Google Scholar]
  5. Gordon A. S., Cooper G. W., Zanjani E. D. The kidney and erythropoiesis. Semin Hematol. 1967 Oct;4(4):337–358. [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Jacobson W., Sidman R. L., Diamond L. K. The effect of testosterone on the uptake of tritiated thymidine by the bone marrow of children. Ann N Y Acad Sci. 1968 Mar 29;149(1):389–405. doi: 10.1111/j.1749-6632.1968.tb15173.x. [DOI] [PubMed] [Google Scholar]
  9. Jepson J. H., Lowenstein L. Inhibition of the stem-cell action of erythropoietin by estradiol. Proc Soc Exp Biol Med. 1966 Nov;123(2):457–460. doi: 10.3181/00379727-123-31513. [DOI] [PubMed] [Google Scholar]
  10. Kappas A., Granick S. Steroid induction of porphyrin synthesis in liver cell culture. II. The effects of heme, uridine diphosphate glucuronic acid, and inhibitors of nucleic acid and protein synthesis on the induction process. J Biol Chem. 1968 Jan 25;243(2):346–351. [PubMed] [Google Scholar]
  11. Kappas A., Song C. S., Levere R. D., Sachson R. A., Granick S. THE INDUCTION OF delta-AMINOLEVULINIC ACID SYNTHETASE in vivo IN CHICK EMBRYO LIVER BY NATURAL STEROIDS. Proc Natl Acad Sci U S A. 1968 Oct;61(2):509–513. doi: 10.1073/pnas.61.2.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Meineke H. A., Crafts R. C. Further observations on the mechanism by which androgens and growth hormone influence erythropoiesis. Ann N Y Acad Sci. 1968 Mar 29;149(1):298–307. [PubMed] [Google Scholar]
  14. Mirand E. A., Gordon A. S. Mechanism of estrogen action in erythropoiesis. Endocrinology. 1966 Feb;78(2):325–332. doi: 10.1210/endo-78-2-325. [DOI] [PubMed] [Google Scholar]
  15. Mirand E. A., Gordon A. S., Wenig J. Mechanism of testosterone action in erythropoiesis. Nature. 1965 Apr 17;206(981):270–272. doi: 10.1038/206270a0. [DOI] [PubMed] [Google Scholar]
  16. Naets J. P., Wittek M. Mechanism of action of androgens on erythropoiesis. Am J Physiol. 1966 Feb;210(2):315–320. doi: 10.1152/ajplegacy.1966.210.2.315. [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. Sanchez-Medal L., Gomez-Leal A., Duarte L., Guadalupe Rico M. Anabolic androgenic steroids in the treatment of acquired aplastic anemia. Blood. 1969 Sep;34(3):283–300. [PubMed] [Google Scholar]
  20. Schooley J. C. Inhibition of erythropoietic stimulation by testosterone in polycythemic mice receiving anti-erythropoietin. Proc Soc Exp Biol Med. 1966 Jun;122(2):402–403. doi: 10.3181/00379727-122-31146. [DOI] [PubMed] [Google Scholar]
  21. TEALE F. W. Cleavage of the haem-protein link by acid methylethylketone. Biochim Biophys Acta. 1959 Oct;35:543–543. doi: 10.1016/0006-3002(59)90407-x. [DOI] [PubMed] [Google Scholar]

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