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. 1975 Dec;55(4):535–539. doi: 10.1111/j.1476-5381.1975.tb07429.x

The influence of metyrapone on the synthesis and release of prostaglandins from the pregnant rat uterus in vitro.

M J Parnham, J M Sneddon
PMCID: PMC1666735  PMID: 813801

Abstract

1 Metyrapone (150 mg/kg, s.c. or i.p.) an inhibitor of corticosteroid biosynthesis, significantly reduced the release of prostaglandins of the F-type from isolated preparations of pregnant rat uteri in vitro, on day 22 - the expected day of delivery. 2 Metyrapone and indomethacin administered in vitro both inhibited the conversion of 14C-arachidonic acid to prostaglandin E2 by homogenates of day 22 pregnant rat uteri. Metyrapone was approximately 150 times less potent than indomethacin. Although indomethacin also inhibited prostaglandin F2alpha production, metyrapone stimulated synthesis of this prostaglandin. The differential inhibition of prostaglandin synthesis by metyrapone may reflect sensitivity of the inhibitor to changes in experimental conditions. 3 Inhibition of prostaglandin synthesis may explain the effects of metyrapone on parturition in the rat.

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Selected References

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

  1. Aiken J. W. Aspirin and indomethacin prolong parturition in rats: evidence that prostaglandins contribute to expulsion of fetus. Nature. 1972 Nov 3;240(5375):21–25. doi: 10.1038/240021a0. [DOI] [PubMed] [Google Scholar]
  2. Blackwell G. J., Flower R. J., Parsons M. F., Vane J. R. Factors influencing the turnover of prostaglandin synthetase. Br J Pharmacol. 1975 Mar;53(3):467P–468P. [PMC free article] [PubMed] [Google Scholar]
  3. CHART J. J., SHEPPARD H. Pharmacology and biochemistry of some amphenone analogues and other adrenal cortical inhibitors. J Med Pharm Chem. 1959 Oct;1:407–441. doi: 10.1021/jm50006a002. [DOI] [PubMed] [Google Scholar]
  4. Chester R., Dukes M., Slater S. R., Walpole A. L. Delay of parturition in the rat by anti-inflammatory agents which inhibit the biosynthesis of prostaglandins. Nature. 1972 Nov 3;240(5375):37–38. doi: 10.1038/240037a0. [DOI] [PubMed] [Google Scholar]
  5. Cohen A. Plasma corticosterone concentration in the foetal rat. Horm Metab Res. 1973 Jan;5(1):66–66. [PubMed] [Google Scholar]
  6. Dunn M. V., Humphries N. G., Judkins G. R., Kendall J. Z., Knight G. W. The effect of prostaglandin F2 antibody on gestation length in the rat. Prostaglandins. 1973 Apr;3(4):509–514. doi: 10.1016/0090-6980(73)90160-3. [DOI] [PubMed] [Google Scholar]
  7. Dupouy J. P. Activité corticostimulante de l'hypophyse du faetus de rat après surrénalectomie maternelle et injection de métopirone à différents stades de la gestation. C R Acad Sci Hebd Seances Acad Sci D. 1972 Jun 26;274(26):3585–3588. [PubMed] [Google Scholar]
  8. Flower R. J., Cheung H. S., Cushman D. W. Quantitative determination of prostaglandins and malondialdehyde formed by the arachidonate oxygenase (prostaglandin synthetase) system of bovine seminal vesicle. Prostaglandins. 1973 Sep;4(3):325–341. doi: 10.1016/0090-6980(73)90020-8. [DOI] [PubMed] [Google Scholar]
  9. GRIFFITHS K. Inhibition of '19-hydroxylase' activity in the golden hamster adrenal by SU4885. J Endocrinol. 1963 Jun;26:445–446. doi: 10.1677/joe.0.0260445. [DOI] [PubMed] [Google Scholar]
  10. Harney P. J., Sneddon J. M., Williams K. I. The influence of ovarian hormones upon the motility and prostaglandin production of the pregnant rat uterus in vitro. J Endocrinol. 1974 Feb;60(2):343–351. doi: 10.1677/joe.0.0600343. [DOI] [PubMed] [Google Scholar]
  11. Kalavsky S. M. Fetal rat adrenal steroidogenesis. Biol Neonate. 1971;17(5):427–435. doi: 10.1159/000240335. [DOI] [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. Liggins G. C., Fairclough R. J., Grieves S. A., Kendall J. Z., Knox B. S. The mechanism of initiation of parturition in the ewe. Recent Prog Horm Res. 1973;29:111–159. doi: 10.1016/b978-0-12-571129-6.50007-5. [DOI] [PubMed] [Google Scholar]
  14. Maddox I. S. The role of copper in prostaglandin synthesis. Biochim Biophys Acta. 1973 Apr 13;306(1):74–81. doi: 10.1016/0005-2760(73)90210-5. [DOI] [PubMed] [Google Scholar]
  15. Matsumoto K., Kotoh K., Miyata J., Kurachi K. Effect of 2-methyl-1,2-bis-(3-pyridyl)-1-propanone (SU 4885) on oestrogen biosynthesis in vivo. J Endocrinol. 1965 Oct;33(2):317–318. doi: 10.1677/joe.0.0330317. [DOI] [PubMed] [Google Scholar]
  16. Nugteren D. H., Hazelhof E. Isolation and properties of intermediates in prostaglandin biosynthesis. Biochim Biophys Acta. 1973 Dec 20;326(3):448–461. doi: 10.1016/0005-2760(73)90145-8. [DOI] [PubMed] [Google Scholar]
  17. Parnham M. J., Sneddon J. M. Proceedings: Metyrapone inhibits prostaglandin synthesis and release from the pregnant rat uterus in vitro. Br J Pharmacol. 1975 Jun;54(2):278P–278P. [PMC free article] [PubMed] [Google Scholar]
  18. Parnham M. J., Sneddon J. M., Williams K. I. Evidence for a possible foetal control of prostaglandin release from the pregnant rat uterus in vitro. J Endocrinol. 1975 Jun;65(3):429–437. doi: 10.1677/joe.0.0650429. [DOI] [PubMed] [Google Scholar]
  19. Parvez H., Roffi J., Parvez S. Gestation prolongée chez des rattes traitées par la métopirone. C R Acad Sci Hebd Seances Acad Sci D. 1972 Jan 10;274(2):262–263. [PubMed] [Google Scholar]
  20. Swaab D. F., Honnebier W. J. The influence of removal of the fetal rat brain upon intrauterine growth of the fetus and the placenta and on gestation length. J Obstet Gynaecol Br Commonw. 1973 Jul;80(7):589–597. doi: 10.1111/j.1471-0528.1973.tb16031.x. [DOI] [PubMed] [Google Scholar]
  21. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  22. Vane J. R., Williams K. I. The contribution of prostaglandin production to contractions of the isolated uterus of the rat. Br J Pharmacol. 1973 Aug;48(4):629–639. doi: 10.1111/j.1476-5381.1973.tb08250.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Williams K. I., Sneddon J. M., Harney P. J. Prostaglandin production by the pregnant rat uterus in vitro and its relevance to parturition. Pol J Pharmacol Pharm. 1974 Jan-Apr;26(1):207–215. [PubMed] [Google Scholar]
  24. Yoshinaga K., Hawkins R. A., Stocker J. F. Estrogen secretion by the rat ovary in vivo during the estrous cycle and pregnancy. Endocrinology. 1969 Jul;85(1):103–112. doi: 10.1210/endo-85-1-103. [DOI] [PubMed] [Google Scholar]

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