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. 1981 Dec 21;9(24):6917–6933. doi: 10.1093/nar/9.24.6917

Hormonal modulation of alpha-fetoprotein gene expression in newborn rat livers.

J F Chiu, R J Massari, C E Schwartz, N T Meisler, J W Thanassi
PMCID: PMC327651  PMID: 6174948

Abstract

Suppression of serum alpha-fetoprotein (AFP) levels in glucocorticoid treated newborn rats was investigated. Daily intraperitoneal injection of 2 micrograms/g body weight of dexamethasone into newborn rats greatly reduced the concentration of AFP in the serum and liver cytosol. In contrast, this treatment stimulated liver ornithine decarboxylase activity. The reduction in AFP levels is not due to a change of distribution of AFP molecular variants, inhibition of secretion of synthesized AFP by the liver or disruption of liver polysomes. Glucocorticoids decrease the AFP levels in hormone-treated rats by supressing the synthesis of AFP. The size of AFP polysomes isolated from the livers of dexamethasone-treated rats were as large as those from normal rats. However, the amount of AFP-producing polysomes in hormone-treated rat liver is only 14% of the controls. By hybridization assays, it was found that dexamethasone treated livers contained decreased amounts of AFP mRNA sequences in liver cytoplasmic and nuclear RNAs. The decreased amounts of AFP mRNA sequences in hormone-treated liver are caused by both a decrease in the rate of AFP mRNA transcription and in AFP mRNA stability.

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Selected References

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

  1. Abelev G. I. Production of embryonal serum alpha-globulin by hepatomas: review of experimental and clinical data. Cancer Res. 1968 Jul;28(7):1344–1350. [PubMed] [Google Scholar]
  2. Adinolfi M., Beck S., Embury S., Polani P. E., Seller M. J. Levels of alpha-fetoprotein in amniotic fluids of mice (curly-tail) with neural tube defects. J Med Genet. 1976 Dec;13(6):511–513. doi: 10.1136/jmg.13.6.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adinolfi M. Human alphafetoprotein 1956-1978. Adv Hum Genet. 1979;9:165–228. [PubMed] [Google Scholar]
  4. Belanger L., Hamel D., Lachance L., Dufour D., Tremblay M., Gagnon P. M. Hormonal regulation of alpha1 foetoprotein. Nature. 1975 Aug 21;256(5519):657–659. doi: 10.1038/256657a0. [DOI] [PubMed] [Google Scholar]
  5. Brock D. J. Prenatal diagnosis of neural tube defects. Eur J Clin Invest. 1977 Dec;7(6):465–472. doi: 10.1111/j.1365-2362.1977.tb01637.x. [DOI] [PubMed] [Google Scholar]
  6. Brown P. C., Papaconstantinou J. Coordinated modulation of albumin synthesis and mRNA levels in cultured hepatoma cells by hydrocortisone and cyclic AMP analogs. J Biol Chem. 1979 Oct 10;254(19):9379–9384. [PubMed] [Google Scholar]
  7. Bélanger L., Commer P., Chiu J. F. Isolation of rat alpha1-fetoprotein messenger RNA from Morris hepatoma 7777. Cancer Res. 1979 Jun;39(6 Pt 1):2141–2148. [PubMed] [Google Scholar]
  8. Bélanger L., Fleischer B., Fleischer S., Guillouzo A., Lemonnier M., Chiu J. F. Subcellular distribution and molecular heterogeneity of alpha 1-fetoprotein in newborn rat liver. Biochemistry. 1979 May 15;18(10):1962–1968. doi: 10.1021/bi00577a018. [DOI] [PubMed] [Google Scholar]
  9. Cain G. D., Mayer G., Jones E. A. Augmentation of albumin but not fibrinogen synthesis by corticosteroids in patients with hepatocellular disease. J Clin Invest. 1970 Dec;49(12):2198–2204. doi: 10.1172/JCI106438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chiu J. F., Decha-Umphai W., Commer P. alpha 1-Fetoprotein mRNA of rat yolk sac and hepatoma. Nucleic Acids Res. 1979 Sep 11;7(1):239–249. doi: 10.1093/nar/7.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Civelli O., Vincent A., Buri J. F., Scherrer K. Evidence for a translational inhibitor linked to globin mRNA in untranslated free cytoplasmic messenger ribonucleoprotein complexes. FEBS Lett. 1976 Dec 15;72(1):71–76. doi: 10.1016/0014-5793(76)80815-0. [DOI] [PubMed] [Google Scholar]
  12. Commer P., Schwartz C., Tracy S., Tamaoki T., Chiu J. F. Dexamethasone inhibits alpha-fetoprotein gene expression in developing mouse liver. Biochem Biophys Res Commun. 1979 Aug 28;89(4):1294–1299. doi: 10.1016/0006-291x(79)92149-1. [DOI] [PubMed] [Google Scholar]
  13. Eloranta T. O., Raina A. M. S-adenosylmethionine metabolism and its relation to polyamine synthesis in rat liver. Effect of nutritional state, adrenal function, some drugs and partial hepatectomy. Biochem J. 1977 Nov 15;168(2):179–185. doi: 10.1042/bj1680179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fodor E. J., Doty P. Highly specific transcription of globin sequences in isolated reticulocyte nuclei. Biochem Biophys Res Commun. 1977 Aug 22;77(4):1478–1485. doi: 10.1016/s0006-291x(77)80145-9. [DOI] [PubMed] [Google Scholar]
  15. Gilboa E., Soreq H., Aviv H. Initiation of RNA synthesis in isolated nuclei. Eur J Biochem. 1977 Jul 15;77(2):393–400. doi: 10.1111/j.1432-1033.1977.tb11679.x. [DOI] [PubMed] [Google Scholar]
  16. Innis M. A., Miller D. L. Quantitation of rat alpha-fetoprotein messenger RNA with a complementary DNA probe. J Biol Chem. 1977 Dec 10;252(23):8469–8475. [PubMed] [Google Scholar]
  17. Innis M. A., Miller D. L. alpha-Fetoprotein gene expression. Control of alpha-fetoprotein mRNA levels in cultured rat hepatoma cells. J Biol Chem. 1979 Sep 25;254(18):9148–9154. [PubMed] [Google Scholar]
  18. Kafatos F. C., Jones C. W., Efstratiadis A. Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure. Nucleic Acids Res. 1979 Nov 24;7(6):1541–1552. doi: 10.1093/nar/7.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Konkel D. A., Ingram V. M. RNA aggregation during sulfhydryl-agarose chromatography of mercurated RNA. Nucleic Acids Res. 1977 Jun;4(6):1979–1988. doi: 10.1093/nar/4.6.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miura K., Law S. W., Nishi S., Tamaoki T. Isolation of alpha-fetoprotein messenger RNA from mouse yolk sac. J Biol Chem. 1979 Jun 25;254(12):5515–5521. [PubMed] [Google Scholar]
  21. Nakamura M., Nakanishi S., Sueoka S., Imura H., Numa S. Effects of steroid hormones on the level of corticotropin messenger RNA activity in cultured mouse-pituitary-tumor cells. Eur J Biochem. 1978 May;86(1):61–66. doi: 10.1111/j.1432-1033.1978.tb12284.x. [DOI] [PubMed] [Google Scholar]
  22. ORNSTEIN L. DISC ELECTROPHORESIS. I. BACKGROUND AND THEORY. Ann N Y Acad Sci. 1964 Dec 28;121:321–349. doi: 10.1111/j.1749-6632.1964.tb14207.x. [DOI] [PubMed] [Google Scholar]
  23. Palacios R., Palmiter R. D., Schimke R. T. Identification and isolation of ovalbumin-synthesizing polysomes. I. Specific binding of 125 I-anti-ovalbumin to polysomes. J Biol Chem. 1972 Apr 25;247(8):2316–2321. [PubMed] [Google Scholar]
  24. Palmiter R. D., Carey N. H. Rapid inactivation of ovalbumin messenger ribonucleic acid after acute withdrawal of estrogen. Proc Natl Acad Sci U S A. 1974 Jun;71(6):2357–2361. doi: 10.1073/pnas.71.6.2357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Panko W. B., Kenney F. T. Hormonal stimulation of hepatic ornithine decarboxylase. Biochem Biophys Res Commun. 1971 Apr 16;43(2):346–350. doi: 10.1016/0006-291x(71)90759-5. [DOI] [PubMed] [Google Scholar]
  26. Roberts J. L., Budarf M. L., Baxter J. D., Herbert E. Selective reduction of proadrenocorticotropin/endorphin proteins and messenger ribonucleic acid activity in mouse pituitary tumor cells by glucocorticoids. Biochemistry. 1979 Oct 30;18(22):4907–4915. doi: 10.1021/bi00589a019. [DOI] [PubMed] [Google Scholar]
  27. Ruoslahti E., Seppälä M. alpha-Fetoprotein in cancer and fetal development. Adv Cancer Res. 1979;29:275–346. doi: 10.1016/s0065-230x(08)60849-0. [DOI] [PubMed] [Google Scholar]
  28. Russell D., Snyder S. H. Amine synthesis in rapidly growing tissues: ornithine decarboxylase activity in regenerating rat liver, chick embryo, and various tumors. Proc Natl Acad Sci U S A. 1968 Aug;60(4):1420–1427. doi: 10.1073/pnas.60.4.1420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sala-Trepat J. M., Dever J., Sargent T. D., Thomas K., Sell S., Bonner J. Changes in expression of albumin and alpha-fetoprotein genes during rat liver development and neoplasia. Biochemistry. 1979 May 29;18(11):2167–2178. doi: 10.1021/bi00578a006. [DOI] [PubMed] [Google Scholar]
  30. Sell S., Nichols M., Becker F. F., Leffert H. L. Hepatocyte proliferation and alpha 1-fetoprotein in pregnant, neonatal, and partially hepatectomized rats. Cancer Res. 1974 Apr;34(4):865–871. [PubMed] [Google Scholar]
  31. Sell S., Thomas K., Michalson M., Salatrepat J., Bonner J. Control of albumin and alpha-fetoprotein expression in rat liver and in some transplantable hepatocellular carcinomas. Biochim Biophys Acta. 1979 Aug 29;564(1):173–178. doi: 10.1016/0005-2787(79)90198-9. [DOI] [PubMed] [Google Scholar]
  32. Shafritz D. A. Protein synthesis with messenger ribonucleic acid fractions from membrane-bound and free liver polysomes. Translation characteristics of liver polysomal ribonucleic acids and evidence for albumin production in a messenger-dependent reticulocyte cell-free system. J Biol Chem. 1974 Jan 10;249(1):81–88. [PubMed] [Google Scholar]
  33. TATARINOV Iu S. OBNARUZHENIE EMBRIOSPETSIFICHESKOGO ALPHA-GLOBULINA V SYVOROTKE KROVI BOL'NOGO PERVICHNYM RAKOM PECHENI. Vopr Med Khim. 1964 Jan-Feb;10:90–91. [PubMed] [Google Scholar]
  34. Tashjian A. H., Jr, Bancroft F. C., Richardson U. I., Goldlust M. B., Rommel F. A., Ofner P. Multiple differentiated functions in an unusual clonal strain of hepatoma cells. In Vitro. 1970 Jul-Aug;6(1):32–45. doi: 10.1007/BF02616132. [DOI] [PubMed] [Google Scholar]
  35. Taylor J. M., Schimke R. T. Specific binding of albumin antibody to rat liver polysomes. J Biol Chem. 1974 Jun 10;249(11):3597–3601. [PubMed] [Google Scholar]
  36. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tomkins G. M., Gelehrter T. D., Granner D., Martin D., Jr, Samuels H. H., Thompson E. B. Control of specific gene expression in higher organisms. Expression of mammalian genes may be controlled by repressors acting on the translation of messenger RNA. Science. 1969 Dec 19;166(3912):1474–1480. doi: 10.1126/science.166.3912.1474. [DOI] [PubMed] [Google Scholar]
  38. Vogt V. M. Purification and further properties of single-strand-specific nuclease from Aspergillus oryzae. Eur J Biochem. 1973 Feb 15;33(1):192–200. doi: 10.1111/j.1432-1033.1973.tb02669.x. [DOI] [PubMed] [Google Scholar]
  39. Waldmann T. A., McIntire K. R. Serum-alpha-fetoprotein levels in patients with ataxia-telangiectasia. Lancet. 1972 Nov 25;2(7787):1112–1115. doi: 10.1016/s0140-6736(72)92717-1. [DOI] [PubMed] [Google Scholar]
  40. Yap S. H., Strair R. K., Shafritz D. A. Effect of a short term fast on the distribution of cytoplasmic albumin messenger ribonucleic acid in rat liver. Evidence for formation of free albumin messenger ribonucleoprotein particles. J Biol Chem. 1978 Jul 25;253(14):4944–4950. [PubMed] [Google Scholar]
  41. Zasloff M., Felsenfeld G. Use of mercury-substituted ribonucleoside triphosphates can lead to artefacts in the analysis of in vitro chromatin transcrits. Biochem Biophys Res Commun. 1977 Apr 11;75(3):598–603. doi: 10.1016/0006-291x(77)91514-5. [DOI] [PubMed] [Google Scholar]
  42. Zähringer J., Konijn A. M., Baliga B. S., Munro H. N. Mechanism of iron induction of ferritin synthesis. Biochem Biophys Res Commun. 1975 Jul 22;65(2):583–590. doi: 10.1016/s0006-291x(75)80186-0. [DOI] [PubMed] [Google Scholar]

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