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. 1970 Oct;67(2):779–785. doi: 10.1073/pnas.67.2.779

Glucocorticoid Inhibition of RNA Synthesis Responsible for Cleft Palate in Mice: A Model*

Ernest F Zimmerman 1,2,3,, Floyd Andrew 1,2,3, Harold Kalter 1,2,3
PMCID: PMC283273  PMID: 5289020

Abstract

A study was undertaken to elucidate the molecular mechanisms by which glucocorticoids induce cleft palate in mice. It was hypothesized that a compound such as triamcinolone acetonide inhibits mRNA synthesis; that this results later in depressed protein synthesis; and that the latter is ultimately responsible for slowed palate formation and cleft palate. Support for the model derives from the fact that the palatine shelves rise and fuse 3-4 days after the most sensitive time of administration of steroid; RNA synthesis was markedly inhibited 6-24 hr after its administration; and coadministration of cycloheximide partially reversed the tendency toward cleft palate formation.

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Selected References

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

  1. Alexander C. S., Swingle K. F., Nagasawa H. T. Teratogenic effect of puromycin aminonucleoside on rat kidney. Nephron. 1966;3(6):344–351. doi: 10.1159/000179551. [DOI] [PubMed] [Google Scholar]
  2. BERNSTEIN J., MEYER R., PICKMAN D. S. Failure of amino-nucleoside to produce abnormalities in the foetus of the rat. Nature. 1962 Sep 22;195:1209–1209. doi: 10.1038/1951209a0. [DOI] [PubMed] [Google Scholar]
  3. Chaube S., Kreis W., Uchida K., Murphy M. L. The teratogenic effect of 1-beta-D-arabinofuranosylcytosine in the rat. Protection by deoxycytidine. Biochem Pharmacol. 1968 Jul;17(7):1213–1216. doi: 10.1016/0006-2952(68)90058-0. [DOI] [PubMed] [Google Scholar]
  4. Chestukhin A. V., Novikova M. A. Vliianie kortizona na sintez nukleinovykh kislot u zarodyshei morskogo ezha. Biokhimiia. 1969 Mar-Apr;34(2):242–248. [PubMed] [Google Scholar]
  5. Church R. B., McCarthy B. J. Ribonucleic acid synthesis in regenerating and embryonic liver. II. The synthesis of RNA during embryonic liver development and its relationship to regenerating liver. J Mol Biol. 1967 Feb 14;23(3):477–486. doi: 10.1016/s0022-2836(67)80119-0. [DOI] [PubMed] [Google Scholar]
  6. Denis H. Gene expression in amphibian development II. Release of the genetic information in growing embryos. J Mol Biol. 1966 Dec 28;22(2):285–304. doi: 10.1016/0022-2836(66)90133-1. [DOI] [PubMed] [Google Scholar]
  7. FRASER F. C., KALTER H., WALKER B. E., FAINSTAT T. D. The experimental production of cleft palate with cortisone and other hormones. J Cell Physiol Suppl. 1954 May;43(Suppl 1):237–259. doi: 10.1002/jcp.1030430411. [DOI] [PubMed] [Google Scholar]
  8. HARRIS J. W. OLIGOHYDRAMNIOS AND CORTISONE-INDUCED CLEFT PALATE. Nature. 1964 Aug 1;203:533–534. doi: 10.1038/203533a0. [DOI] [PubMed] [Google Scholar]
  9. JACOBS R. M. S35--LIQUID--SCINTILLATION COUNT ANALYSIS OF MORPHOGENESIS AND TERATOGENESIS OF THE PALATE IN MOUSE EMBRYOS. Anat Rec. 1964 Nov;150:271–277. doi: 10.1002/ar.1091500309. [DOI] [PubMed] [Google Scholar]
  10. Jacobs R. M. Effects of cortisone acetate upon hydration of embryonic palate in two inbred strains of mice. Anat Rec. 1966 Sep;156(1):1–4. doi: 10.1002/ar.1091560102. [DOI] [PubMed] [Google Scholar]
  11. KALTER H., FRASER F. C. Production of congenital defects in the offspring of pregnant mice treated with compound F. Nature. 1952 Apr 19;169(4303):665–665. doi: 10.1038/169665a0. [DOI] [PubMed] [Google Scholar]
  12. Kalter H. The Inheritance of Susceptibility to the Teratogenic Action of Cortisone in Mice. Genetics. 1954 Mar;39(2):185–196. doi: 10.1093/genetics/39.2.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LARSSON K. S. Studies on the closure of the secondary palate. IV. Autoradiographic and histochemical studies of mouse embryos from cortisone-treated mothers. Acta Morphol Neerl Scand. 1962;4:369–386. [PubMed] [Google Scholar]
  14. Makman M. H., Dvorkin B., White A. Alterations in protein and nucleic acid metabolism of thymocytes produced by adrenal steroids in vitro. J Biol Chem. 1966 Apr 10;241(7):1646–1648. [PubMed] [Google Scholar]
  15. Nakagawa S., White A. Acute decrease in RNA polymerase activity of rat thymus in response to cortisol injection. Proc Natl Acad Sci U S A. 1966 Apr;55(4):900–904. doi: 10.1073/pnas.55.4.900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Peterkofsky B., Tomkins G. M. Evidence for the steroid-induced accumulation of tyrosine-aminotransferase messenger RNA in the absence of protein synthesis. Proc Natl Acad Sci U S A. 1968 May;60(1):222–228. doi: 10.1073/pnas.60.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pratt W. B., Aronow L. The effect of glucocorticoids on protein and nucleic acid synthesis in mouse fibroblasts growing in vitro. J Biol Chem. 1966 Nov 25;241(22):5244–5250. [PubMed] [Google Scholar]
  18. SEGAL H. L., KIM Y. S. GLUCOCORTICOID STIMULATION OF THE BIOSYNTHESIS OF GLUTAMIC-ALANINE TRANSAMINASE. Proc Natl Acad Sci U S A. 1963 Nov;50:912–918. doi: 10.1073/pnas.50.5.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schimke R. T., Sweeney E. W., Berlin C. M. An analysis of the kinetics of rat liver tryptophan pyrrolase induction: the significance of both enzyme synthesis and degradation. Biochem Biophys Res Commun. 1964 Mar 26;15(3):214–219. doi: 10.1016/0006-291x(64)90148-2. [DOI] [PubMed] [Google Scholar]
  20. Spirin A. S., Nemer M. Messenger RNA in early sea-urchin embryos: cytoplasmic particles. Science. 1965 Oct 8;150(3693):214–217. doi: 10.1126/science.150.3693.214. [DOI] [PubMed] [Google Scholar]
  21. Walker B. E. Cleft Palate Produced in Mice by Human-Equivalent Dosage with Triamcinolone. Science. 1965 Aug 20;149(3686):862–863. doi: 10.1126/science.149.3686.862. [DOI] [PubMed] [Google Scholar]
  22. Whiteley A. H., McCarthy B. J., Whiteley H. R. Changing populations of messenger RNA during sea urchin development. Proc Natl Acad Sci U S A. 1966 Mar;55(3):519–525. doi: 10.1073/pnas.55.3.519. [DOI] [PMC free article] [PubMed] [Google Scholar]

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