the g-doc

the g-doc

Explore health topics

Late effect of estrogen on endotoxin response in the rat - The Journal of Laboratory and Clinical Medicine


This paper is only available as a PDF. To read, Please Download here.

Abstract

The lethal effect of small doses of bacterial endotoxin on many species is well known. We have previously demonstrated that a preparation of conjugated estrogens protects rats against this effect when administered up to an hour before an injection of E. coli endotoxin. Further study has shown that this protective effect is lost and indeed reversed with time. When the period between the estrogen and endotoxin injections was lengthened to between 18 and 48 hours, a marked enhancement of sensitivity was encountered. This paradoxical increase in endotoxin sensitivity reduced the L.D. 50 approximately tenfold and occurred in both males and females. The male animals were, however, more resistant. Tissue changes were those associated with severe endotoxin shock. No fibrin deposition could be seen and the ineffectiveness of heparin in preventing death was viewed as further evidence that a Shwartzman type of reaction was not responsible. The failure of hydrocortisone or ACTH to modify the reaction when injected just prior to endotoxin challenge makes adrenal suppression an unlikely mechanism. The effect of pretreating with estrogens 24 hours before endotoxin administration rendered ineffective a usually protective dose of conjugated estrogens given just before the challenge. Measuring the clearance of I131-labeled microaggregated albumin, no significant alteration in reticuloendothelial function could be demonstrated 24 hours after a single estrogen dose. When individual estrogens were compared, estriol proved to be the most potent. The possible significance of enhancement of endotoxin toxicity by estrogens in explaining some pathological features of pregnancy is discussed. It is also suggested that hepatic dysfunction encountered with estrogen administration may be a related phenomenon.
To read this article in full you will need to make a payment

Purchase one-time access:

Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
  • For academic or personal research use, select 'Academic and Personal'
  • For corporate R&D use, select 'Corporate R&D Professionals'

Subscribe:

Subscribe to Translational Research
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Institutional Access: Sign in to ScienceDirect

References

  1. 1.
    • Nolan J.P.
    Protective action of oestrogen against the lethal effect of endotoxin in the rat.
    Nature. 1967; 213: 201
  2. 1.
    • Iio M. •
    • Wagner H.N.
    Studies of the reticuloendothelial system (R.E.S.) I. Measurement of the phagocytic capacity of the R.E.S. in man and dog.
    J. Clin. Invest. 1963; 42: 417
  3. 1.
    • Nicol T. •
    • Bilbey D.L.G. •
    • Cordingly J. •
    • Druce C.
    Response of the R.E.S. to stimulation with oestrogens.
    Nature. 1961; 192: 978
  4. 1.
    • Levin J. •
    • Cluff L.E.
    Endotoxemia and adrenal hemorrhage, a mechanism for the Waterhouse-Friderichsen syndrome.
    J. Exper. Med. 1965; 121: 247
  5. 1.
    • Bernstein D.E.
    Autotransplantation of the adrenal to the portal circulation: Further evidence for the dependency of adrenal hypertrophy on estrogen.
    Endocrinology. 1964; 74: 661
  6. 1.
    • Levitin H. •
    • Kendrick M.I. •
    • Kass E.H.
    Effect of route of administration on protective action of corticosterone and cortisol against endotoxin.
    in: Proc. Soc. Exper. Biol. & Med. 93. 1956: 306
  7. 1.
    • Gronvall J.A. •
    • Brunson J.G.
    The generalized Shwartzman phenomenon in rats.
    Arch. Path. 1956; 62: 324
  8. 1.
    • Wong T.C.
    A study of the generalized Shwartzman reaction in pregnant rats induced by bacterial endotoxin.
    Am. J. Obst. & Gynec. 1962; 84: 786
  9. 1.
    • Apitz K.
    A study of the generalized Shwartzman phenomenon.
    J. Immunol. 1935; 29: 255
  10. 1.
    • Freedman H.H. •
    • Sultzer B.M.
    Aspects of endotoxin tolerance: Phagocytosis and specificity.
    in: Landy M. Braun W. Bacterial endotoxins. Boden Co, Rahway1964: 537
  11. 1.
    • Nolan J.P. •
    • O'Connell C.J.
    Vascular response in the isolated rat liver. I. Endotoxin, direct effects.
    J. Exper. Med. 1965; 122: 1063
  12. 1.
    • Jacobson E. •
    • Mehlman B. •
    • Kalas J.
    Vasoactive mediators as the "trigger mechanism" of endotoxin shock.
    J. Clin. Invest. 1964; 43: 1000
  13. 1.
    • Smith O.W.
    Free and conjugated estrogens in blood and urine before and during parturition in normal human pregnancy.
    Acta endocrinol. 1966; 51
  14. 1.
    • McKay D.G. •
    • Wong T.C.
    The effect of bacterial endotoxin on the placenta of the rat.
    Am. J. Path. 1963; 42: 357
  15. 1.
    • McKay D.G. •
    • Merrill S.J. •
    • Weiner A.E. •
    • Hertig A.T. •
    • Reid D.E.
    The pathologic anatomy of eclampsia, bilateral renal cortical necrosis, pituitary necrosis, and other acute fatal complications of pregnancy, and its possible relationship to the generalized Shwartzman phenomenon.
    Am. J. Obst. & Gynec. 1953; 66: 507
  16. 1.
    • Jones W.A. •
    • Cohen R.B.
    The effect of estrogen on the liver in murine viral hepatitis.
    Am. J. Path. 1963; 42: 237
  17. 1.
    • Bearn A.G. •
    • Kunkel H.G. •
    • Slater R.J.
    The problem of chronic liver disease in young women.
    Am. J. Med. 1956; 21: 3
  18. 1.
    • Combes B. •
    • Shibata H. •
    • Adams R. •
    • Mitchell B.D. •
    • Trammel V.
    Alterations in sulfobromophthalein sodium removal mechanisms from blood during normal pregnancy.
    J. Clin. Invest. 1963; 42: 1431
  19. 1.
    • Mueller M.N. •
    • Kappas A.
    Estrogen pharmacology. I. The influence of estradiol and estriol on hepatic disposal of sulfobromophthalein (B.S.P.) in man.
    J. Clin. Invest. 1964; 43: 1905
  20. 1.
    • Thulin K.E. •
    • Nermark J.
    Seven cases of jaundice in women taking an oral contraceptive, Anovular.
    Brit. M. J. 1966; 1: 584

Article info

Publication history

Accepted: November 14, 1967
Received: October 9, 1967

Footnotes

☆This investigation was supported by United States Public Health Service Grant 1 RO1 AM-9524-01A1 and by The John A. Hartford Foundation.

☆☆A preliminary report of this work was delivered at a meeting of the Federation of American Societies for Experimental Biology in Chicago, April 20, 1967.

★Dr. Anthony Prezyna reviewed the pathological sections, and Dr. John B. Jewell of Ayerst Laboratories supplied the Premarin used in these studies.

Copyright

© 1968 Published by Elsevier Inc.

Related Articles

Published by the g-doc on