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. 1975 Jun;72(6):2279–2283. doi: 10.1073/pnas.72.6.2279

Nature of the increase in renal ornithine decarboxylase activity after cycloheximide administration in the rat.

J H Levine, W E Nicholson, D N Orth
PMCID: PMC432741  PMID: 806079

Abstract

The present study was designed to determine whether the increase in rat renal ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity after cycloheximide administration was a primary effect on the kidney or was a secondary effect of adrenal or pituitary hormones released in response to the drug. Renal ornithine decarboxylase activity was reduced approximately 70% 1 hr after intraperitoneal administration of doses of cycloheximide that also inhibited renal protein synthesis by 68-95% within 1 hr. Protein synthesis began to recover by the second hour, accompanied by a rise in decarboxylase activity that reached a peak about six times greater than pretreatment values at 8 hr, then gradually declined to preinjection levels by 16 hr. Peak ornithine decarboxylase activity was directly proportional to cycloheximide doses up to 250 mug; larger doses, which almost abolished protein synthesis for 8 hr, where inhibitory. Plasma corticosterone rose rapidly after cycloheximide, reached a peak at 2 hr, then fell to baseline by 8 hr. Corticosterone response was also dose-dependent up to 250 mug, but larger doses were inhibitorymadrenalectomy did not reduce decarboxylase activity response to cycloheximide, nor did cortisol administration enhance it. Hypophysectomy greatly reduced baseline renal decarboxylase activity within 9 hr and all but abolished the increase in enzyme activity normally seen after cycloheximide administration to the intact rat. The hypophysectomized animal exhibited apparent increased sensitivity to cycloheximide, since a smaller dose of the drug caused a reduction in renal protein synthesis similar to that seen with a larger dose in the intact rat. As protein synthesis was recovering in the hypophysectomized animals, renal decarboxylase activity responded adequately to the injection of a crude pituitary extract. These data suggest that renal ornithine decarboxylase turnover is rapid, that baseline activity is.maintained by new protein synthesis, and that the increase in renal enzyme activity after cycloheximide is in larger part dependent upon pituitary hormone action.

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Selected References

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

  1. Beck W. T., Bellantone R. A., Canellakis E. S. Puromycin stimulation of rat liver ornithine decarboxylase activity. Nature. 1973 Jan 26;241(5387):275–277. doi: 10.1038/241275a0. [DOI] [PubMed] [Google Scholar]
  2. Brandt J. T., Pierce D. A., Fausto N. Ornithine decarboxylase activity and polyamine synthesis during kidney hypertrophy. Biochim Biophys Acta. 1972 Aug 18;279(1):184–193. doi: 10.1016/0304-4165(72)90253-x. [DOI] [PubMed] [Google Scholar]
  3. FERGUSON J. J., Jr PROTEIN SYNTHESIS AND ADRENOCORTICOTROPIN RESPONSIVENESS. J Biol Chem. 1963 Aug;238:2754–2759. [PubMed] [Google Scholar]
  4. Fausto N. RNA and amine synthesis in the liver of rats given injections of thioacetamide. Cancer Res. 1970 Jul;30(7):1947–1952. [PubMed] [Google Scholar]
  5. Fausto N. Studies on ornithine decarboxylase activity in normal and regenerating livers. Biochim Biophys Acta. 1969 Sep 17;190(1):193–201. doi: 10.1016/0005-2787(69)90168-3. [DOI] [PubMed] [Google Scholar]
  6. Fausto N. The control of ornithine decarboxylase activity during liver regeneration. Biochim Biophys Acta. 1971 Apr 29;238(1):116–128. doi: 10.1016/0005-2787(71)90015-3. [DOI] [PubMed] [Google Scholar]
  7. Garren L. D., Ney R. L., Davis W. W. Studies on the role of protein synthesis in the regulation of corticosterone production by adrenocorticotropic hormone in vivo. Proc Natl Acad Sci U S A. 1965 Jun;53(6):1443–1450. doi: 10.1073/pnas.53.6.1443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hogan B. L. Effect of growth conditions on the ornithine decarboxylase activity of rat hepatoma cells. Biochem Biophys Res Commun. 1971 Oct 15;45(2):301–307. doi: 10.1016/0006-291x(71)90818-7. [DOI] [PubMed] [Google Scholar]
  9. Hölttä E., Raina A. Stimulation of ornithine decarboxylase and nuclear RNA polymerase activity in rat liver by glucagon and dibutyryl cyclic amp. Acta Endocrinol (Copenh) 1973 Aug;73(4):794–800. doi: 10.1530/acta.0.0730794. [DOI] [PubMed] [Google Scholar]
  10. Jänne J., Raina A., Siimes M. Mechanism of stimulation of polyamine synthesis by growth hormone in rat liver. Biochim Biophys Acta. 1968 Sep 24;166(2):419–426. doi: 10.1016/0005-2787(68)90230-x. [DOI] [PubMed] [Google Scholar]
  11. Kaye A. M., Icekson I., Lamprecht S. A., Gruss R., Tsafriri A., Lindner H. R. Stimulation of ornithine decarboxylase activity by luteinizing hormone in immature and adult rat ovaries. Biochemistry. 1973 Jul 31;12(16):3072–3076. doi: 10.1021/bi00740a020. [DOI] [PubMed] [Google Scholar]
  12. Kowal J. ACTH and the metabolism of adrenal cell cultures. Recent Prog Horm Res. 1970;26:623–687. doi: 10.1016/b978-0-12-571126-5.50020-0. [DOI] [PubMed] [Google Scholar]
  13. Levine J. H., Nicholson W. E., Liddle G. W., Orth D. N. Stimulation of adrenal ornithine decarboxylase by adrenocorticotropin and growth hormone. Endocrinology. 1973 Apr;92(4):1089–1095. doi: 10.1210/endo-92-4-1089. [DOI] [PubMed] [Google Scholar]
  14. Morris D. R., Pardee A. B. A biosynthetic ornithine decarboxylase in Escherichia coli. Biochem Biophys Res Commun. 1965 Sep 22;20(6):697–702. doi: 10.1016/0006-291x(65)90072-0. [DOI] [PubMed] [Google Scholar]
  15. Nicholson W. E., Van Loon G. R. Some practical innovations in the biological assay of adrenocorticotropic hormone (ACTH). J Lab Clin Med. 1973 May;81(5):803–808. [PubMed] [Google Scholar]
  16. Ono M., Inoue H., Suzuki F., Takeda Y. Studies on ornithine decarboxylase from the liver of thioacetamide-treated rats. Purification and some properties. Biochim Biophys Acta. 1972 Sep 19;284(1):285–297. doi: 10.1016/0005-2744(72)90067-8. [DOI] [PubMed] [Google Scholar]
  17. Richman R., Dobbins C., Voina S., Underwood L., Mahaffee D., Gitelman, Van Wyk J., Ney R. L. Regulation of adrenal ornithine decarboxylase by adrenocorticotropic hormone and cyclic AMP. J Clin Invest. 1973 Aug;52(8):2007–2015. doi: 10.1172/JCI107385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Russell D. H. Drug stimulation of putrescine and spermidine syntheses. Relationships to enhancement of ribonucleic acid synthesis. Biochem Pharmacol. 1971 Dec;20(12):3481–3491. doi: 10.1016/0006-2952(71)90453-9. [DOI] [PubMed] [Google Scholar]
  19. Russell D. H., Snyder S. H. Amine synthesis in regenerating rat liver: extremely rapid turnover of ornithine decarboxylase. Mol Pharmacol. 1969 May;5(3):253–262. [PubMed] [Google Scholar]
  20. Russell D. H., Snyder S. H., Medina V. J. Growth hormone induction of ornithine decarboxylase in rat liver. Endocrinology. 1970 Jun;86(6):1414–1419. doi: 10.1210/endo-86-6-1414. [DOI] [PubMed] [Google Scholar]
  21. Russell D. H., Taylor R. L. Polyamine synthesis and accumulation in the castrated rat uterus after estradiol-17-beta stimulation. Endocrinology. 1971 Jun;88(6):1397–1403. doi: 10.1210/endo-88-6-1397. [DOI] [PubMed] [Google Scholar]
  22. SIEKEVITZ P. Uptake of radioactive alanine in vitro into the proteins of rat liver fractions. J Biol Chem. 1952 Apr;195(2):549–565. [PubMed] [Google Scholar]
  23. Schimke R. T., Ganschow R., Doyle D., Arias I. M. Regulation of protein turnover in mammalian tissues. Fed Proc. 1968 Sep-Oct;27(5):1223–1230. [PubMed] [Google Scholar]
  24. Sogani R. K., Matsushita S., Mueller J. F., Raben M. S. Stimulation of ornithine decarboxylase activity in rat tissues by growth hormone and by serum growth factor from rats infested with spargana of Spirometra mansonoides. Biochim Biophys Acta. 1972 Sep 15;279(2):377–386. doi: 10.1016/0304-4165(72)90156-0. [DOI] [PubMed] [Google Scholar]

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