Abstract
The effect of dexamethasone on rat alpha-fetoprotein (AFP) expression has been further examined. Quantitation of serum AFP levels from newborns treated with dexamethasone showed a dose-response relationship between the quantity of dexamethasone administered and the reduction in AFP serum level. RNA blots, utilizing cloned AFP cDNA as probe, showed a marked reduction in AFP mRNA in dexamethasone treated livers. The extent of AFP mRNA depletion was correlated with dexamethasone dosage. The effect of dexamethasone on AFP mRNA concentration was relatively rapid; a substantial reduction occurred 12 hours after a single injection. The effect of dexamethasone appeared to be irreversible as hormone withdrawal did not cause AFP mRNA levels to rise. One putative AFP nuclear RNA precursor was identified which rapidly disappeared following dexamethasone treatment. AFP mRNA synthesis was also diminished in nuclei transcribed in vitro. The direct inhibitory effect of glucocorticoid hormone on AFP gene transcription was demonstrated in a reconstituted cell-free nuclear system.
Full text
PDF

















Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ABELEV G. I., PEROVA S. D., KHRAMKOVA N. I., POSTNIKOVA Z. A., IRLIN I. S. Production of embryonal alpha-globulin by transplantable mouse hepatomas. Transplantation. 1963 Apr;1:174–180. doi: 10.1097/00007890-196301020-00004. [DOI] [PubMed] [Google Scholar]
- Abelev G. I. Alpha-fetoprotein in ontogenesis and its association with malignant tumors. Adv Cancer Res. 1971;14:295–358. doi: 10.1016/s0065-230x(08)60523-0. [DOI] [PubMed] [Google Scholar]
- Andrews G. K., Janzen R. G., Tamaoki T. Stability of alpha-fetoprotein messenger RNA in mouse yolk sac. Dev Biol. 1982 Jan;89(1):111–116. doi: 10.1016/0012-1606(82)90299-8. [DOI] [PubMed] [Google Scholar]
- Banerji A., Kalimi M. Development of an [3H] glucocorticoid exchange assay in rat liver cytosol. Steroids. 1981 Apr;37(4):409–421. doi: 10.1016/0039-128x(81)90043-x. [DOI] [PubMed] [Google Scholar]
- Bassett J. M., Thorburn G. D. Foetal plasma corticosteroids and the initiation of parturition in sheep. J Endocrinol. 1969 Jun;44(2):285–286. doi: 10.1677/joe.0.0440285. [DOI] [PubMed] [Google Scholar]
- Bélanger L., Frain M., Baril P., Gingras M. C., Bartkowiak J., Sala-Trepat J. M. Glucocorticosteroid suppression of alpha1-fetoprotein synthesis in developing rat liver. Evidence for selective gene repression at the transcriptional level. Biochemistry. 1981 Nov 10;20(23):6665–6672. doi: 10.1021/bi00526a022. [DOI] [PubMed] [Google Scholar]
- Chen C. L., Feigelson P. Glucocorticoid induction of alpha2u-globulin protein synthesis and its mRNA in rat hepatocytes in vitro. J Biol Chem. 1978 Nov 10;253(21):7880–7885. [PubMed] [Google Scholar]
- Chiu J. F., Huang D. P., Burkhardt A. L., Cote G., Schwartz C. E. The alteration of gene expression in rat liver during chemical carcinogenesis. Arch Biochem Biophys. 1983 Apr 1;222(1):310–320. doi: 10.1016/0003-9861(83)90528-3. [DOI] [PubMed] [Google Scholar]
- Chiu J. F., Massari R. J., Schwartz C. E., Meisler N. T., Thanassi J. W. Hormonal modulation of alpha-fetoprotein gene expression in newborn rat livers. Nucleic Acids Res. 1981 Dec 21;9(24):6917–6933. doi: 10.1093/nar/9.24.6917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chou J. Y., Mano T., Feldman M. Inhibition of synthesis of alpha-fetoprotein by glucocorticoids in cultured hepatoma cells. J Cell Biol. 1982 May;93(2):314–317. doi: 10.1083/jcb.93.2.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cidlowski J. A., Cidlowski N. B. Regulation of glucocorticoid receptors by glucocorticoids in cultured HeLa S3 cells. Endocrinology. 1981 Dec;109(6):1975–1982. doi: 10.1210/endo-109-6-1975. [DOI] [PubMed] [Google Scholar]
- Claire M., Oblin M. E., Steimer J. L., Nakane H., Misumi J., Michaud A., Corvol P. Effect of adrenalectomy and aldosterone on the modulation of mineralocorticoid receptors in rat kidney. J Biol Chem. 1981 Jan 10;256(1):142–147. [PubMed] [Google Scholar]
- 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]
- Ernest M. J., Chen C. L., Feigelson P. Induction of tyrosine aminotransferase synthesis in isolated liver cell suspensions. Absolute dependence of induction on glucocorticoids and glucagon or cyclic AMP. J Biol Chem. 1977 Oct 10;252(19):6783–6791. [PubMed] [Google Scholar]
- Freeman A. E., Engvall E., Hirata K., Yoshida Y., Kottel R. H., Hilborn V., Ruoslahti E. Differentiation of fetal liver cells in vitro. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3659–3663. doi: 10.1073/pnas.78.6.3659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorin M. B., Cooper D. L., Eiferman F., van de Rijn P., Tilghman S. M. The evolution of alpha-fetoprotein and albumin. I. A comparison of the primary amino acid sequences of mammalian alpha-fetoprotein and albumin. J Biol Chem. 1981 Feb 25;256(4):1954–1959. [PubMed] [Google Scholar]
- Guertin M., Baril P., Bartkowiak J., Anderson A., Bélanger L. Rapid suppression of alpha 1-fetoprotein gene transcription by dexamethasone in developing rat liver. Biochemistry. 1983 Aug 30;22(18):4296–4302. doi: 10.1021/bi00287a021. [DOI] [PubMed] [Google Scholar]
- Harmon J. M., Eisen H. J., Brower S. T., Simons S. S., Jr, Langley C. L., Thompson E. B. Identification of human leukemic glucocorticoid receptors using affinity labeling and anti-human glucocorticoid receptor antibodies. Cancer Res. 1984 Oct;44(10):4540–4547. [PubMed] [Google Scholar]
- Huang D. P., Cote G. J., Ho K. L., Chiu J. F. The enhancement of specific gene transcription in isolated nuclei by added HeLa whole cell extract. Int J Biochem. 1984;16(9):963–969. doi: 10.1016/0020-711x(84)90112-5. [DOI] [PubMed] [Google Scholar]
- Huang D. P., Schwartz C. E., Chiu J. F., Cook J. R. Dexamethasone inhibition of rat hepatoma growth and alpha-fetoprotein synthesis. Cancer Res. 1984 Jul;44(7):2976–2980. [PubMed] [Google Scholar]
- Ingram R. S., Scott R. W., Tilghman S. M. alpha-Fetoprotein and albumin genes are in tandem in the mouse genome. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4694–4698. doi: 10.1073/pnas.78.8.4694. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Iynedjian P. B., Jacot M. M. Coordinate induction of several mRNA species in rat kidney during glucocorticoid treatment. J Biol Chem. 1981 Jul 10;256(13):7068–7076. [PubMed] [Google Scholar]
- 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]
- Landes G. M., Villeponteau B., Pribyl T. M., Martinson H. G. Hemoglobin switching in chickens. Is the switch initiated post-transcriptionally? J Biol Chem. 1982 Sep 25;257(18):11008–11014. [PubMed] [Google Scholar]
- Laurell C. B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem. 1966 Apr;15(1):45–52. doi: 10.1016/0003-2697(66)90246-6. [DOI] [PubMed] [Google Scholar]
- Liao W. S., Conn A. R., Taylor J. M. Changes in rat alpha 1-fetoprotein and albumin mRNA levels during fetal and neonatal development. J Biol Chem. 1980 Nov 10;255(21):10036–10039. [PubMed] [Google Scholar]
- Liao W. S., Ricca G. A., Taylor J. M. Cloning of rat alpha-fetoprotein 3'-terminal complementary deoxyribonucleic acid sequences and preparation of radioactively labeled hybridization probes from cloned deoxyribonucleic acid inserts. Biochemistry. 1981 Mar 17;20(6):1646–1652. doi: 10.1021/bi00509a037. [DOI] [PubMed] [Google Scholar]
- Macdonald A. Topical corticosteroid preparations. Hazards and side-effects. Br J Clin Pract. 1971 Sep;25(9):421–425. [PubMed] [Google Scholar]
- Manley J. L., Fire A., Cano A., Sharp P. A., Gefter M. L. DNA-dependent transcription of adenovirus genes in a soluble whole-cell extract. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3855–3859. doi: 10.1073/pnas.77.7.3855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mierendorf R. C., Jr, Mueller G. C. The effect of dexamethasone on the initiation of beta-globin gene transcription in differentiating Friend cells. J Biol Chem. 1982 Apr 25;257(8):4496–4500. [PubMed] [Google Scholar]
- Mitchell B. F., Serón-Ferré M., Hess D. L., Jaffe R. B. Cortisol production and metabolism in the late gestation rhesus monkey fetus. Endocrinology. 1981 Mar;108(3):916–924. doi: 10.1210/endo-108-3-916. [DOI] [PubMed] [Google Scholar]
- Nahon J. L., Gal A., Frain M., Sell S., Sala-Trepat J. M. No evidence for post-transcriptional control of albumin and alpha-fetoprotein gene expression in developing rat liver neoplasia. Nucleic Acids Res. 1982 Mar 25;10(6):1895–1911. doi: 10.1093/nar/10.6.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakanishi S., Kita T., Taii S., Imura H., Numa S. Glucocorticoid effect on the level of corticotropin messenger RNA activity in rat pituitary. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3283–3286. doi: 10.1073/pnas.74.8.3283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raynaud-Jammet C., Baulieu E. E. Action de l'oestradiol in vitro: augmentation de la biosynthèse d'acide ribonucléique dnas les noyaux utérins. C R Acad Sci Hebd Seances Acad Sci D. 1969 Jun 30;268(26):3211–3214. [PubMed] [Google Scholar]
- 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]
- Rokowski R. J., Sheehy J., Cutroneo K. R. Glucocorticoid-mediated selective reduction of functioning collagen messenger ribonucleic acid. Arch Biochem Biophys. 1981 Aug;210(1):74–81. doi: 10.1016/0003-9861(81)90165-x. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Sargent T. D., Wu J. R., Sala-Trepat J. M., Wallace R. B., Reyes A. A., Bonner J. The rat serum albumin gene: analysis of cloned sequences. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3256–3260. doi: 10.1073/pnas.76.7.3256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz C. E., Burkhardt A. L., Huang D. P., Chiu J. F. The effects of dexamethasone on alpha-fetoprotein and albumin synthesis in cultured hepatoma 7777 cells. Biosci Rep. 1982 Oct;2(10):777–784. doi: 10.1007/BF01114937. [DOI] [PubMed] [Google Scholar]
- Scott R. W., Tilghman S. M. Transient expression of a mouse alpha-fetoprotein minigene: deletion analyses of promoter function. Mol Cell Biol. 1983 Jul;3(7):1295–1309. doi: 10.1128/mcb.3.7.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sell S., Becker F. F. alpha-Fetoprotein. J Natl Cancer Inst. 1978 Jan;60(1):19–26. doi: 10.1093/jnci/60.1.19. [DOI] [PubMed] [Google Scholar]
- Sterling K. M., Jr, Harris M. J., Mitchell J. J., DiPetrillo T. A., Delaney G. L., Cutroneo K. R. Dexamethasone decreases the amounts of type I procollagen mRNAs in vivo and in fibroblast cell cultures. J Biol Chem. 1983 Jun 25;258(12):7644–7647. [PubMed] [Google Scholar]
- Taylor R. N., Smith R. G. Effects of highly purified estrogen receptors on gene transcription in isolated nuclei. Biochemistry. 1982 Apr 13;21(8):1781–1787. doi: 10.1021/bi00537a013. [DOI] [PubMed] [Google Scholar]
- Taylor R. N., Smith R. G. Pure estrogen receptor complexes stimulate RNA transcription in vitro. Biochem Biophys Res Commun. 1979 Nov 14;91(1):136–142. doi: 10.1016/0006-291x(79)90594-1. [DOI] [PubMed] [Google Scholar]
- 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]
- Tilghman S. M., Belayew A. Transcriptional control of the murine albumin/alpha-fetoprotein locus during development. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5254–5257. doi: 10.1073/pnas.79.17.5254. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinstock R., Sweet R., Weiss M., Cedar H., Axel R. Intragenic DNA spacers interrupt the ovalbumin gene. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1299–1303. doi: 10.1073/pnas.75.3.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]