Abstract
The plasma concentration of fibrinogen, one of the major acute-phase proteins produced by the liver, increases during the acute-phase response as a result of enhanced synthesis in liver. Since adrenal-cortical hormones have been thought to have a key role in the regulation of the fibrinogen synthesis, fibrinogen-polypeptide mRNA sequences were determined in the present study, by using a specific complementary-DNA probe, in RNA fractions obtained from rat hepatocytes exposed to glucocorticoids in vitro (hepatocyte suspension cultures) and in vivo. Maximal induction of the fibrinogen-polypeptide mRNA (to 400% of the control value) was found in vitro at 0.1 microM-dexamethasone after 9 h of incubation. The same magnitude of induction was obtained with 20 microM-cortisol or 60 microM-corticosterone. In contrast with the findings in vitro, no induction of the fibrinogen-polypeptide mRNA was observed in the liver at various times after injection of different doses of glucocorticoids into rats. These results suggest that more complex regulatory mechanisms are involved and that glucocorticoids are not the sole regulatory factors in vivo in the enhanced synthesis of fibrinogen during the acute-phase response.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Crabtree G. R., Kant J. A. Coordinate accumulation of the mRNAs for the alpha, beta, and gamma chains of rat fibrinogen following defibrination. J Biol Chem. 1982 Jul 10;257(13):7277–7279. [PubMed] [Google Scholar]
- Crane L. J., Miller D. L. A solid-phase radioimmunoassay for fibrinogen. Anal Biochem. 1975 Mar;64(1):60–67. doi: 10.1016/0003-2697(75)90404-2. [DOI] [PubMed] [Google Scholar]
- Crane L. J., Miller D. L. Plasma protein synthesis by isolated rat hepatocytes. J Cell Biol. 1977 Jan;72(1):11–25. doi: 10.1083/jcb.72.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Franks J. J., Kirsch R. E., Frith L. O., Purves L. R., Franks W. T., Franks J. A., Mason P., Saunders S. J. Effect of fibrinogenolytic products D and E on fibrinogen and albumin synthesis in the rat. J Clin Invest. 1981 Feb;67(2):575–580. doi: 10.1172/JCI110069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gordon A. H., Limaos E. A. Effects of bacterial endotoxin and corticosteroids on plasma concentrations of alpha 2 macroglobulin, haptoglobin and fibrinogen in rats. Br J Exp Pathol. 1979 Aug;60(4):434–440. [PMC free article] [PubMed] [Google Scholar]
- Grieninger G., Hertzberg K. M., Pindyck J. Fibrinogen synthesis in serum-free hepatocyte cultures: stimulation by glucocorticoids. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5506–5510. doi: 10.1073/pnas.75.11.5506. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hertzberg K. M., Pindyck J., Mosesson M. W., Grieninger G. Thyroid hormone stimulation of plasma protein synthesis in cultured hepatocytes. J Biol Chem. 1981 Jan 25;256(2):563–566. [PubMed] [Google Scholar]
- Jeejeebhoy K. N., Bruce-Robertson A., Ho J., Sodtke U. The effect of cortisol on the synthesis of rat plasma albumin, fibrinogen and transferrin. Biochem J. 1972 Nov;130(2):533–538. doi: 10.1042/bj1300533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- John D. W., Miller L. L. Regulation of net biosynthesis of serum albumin and acute phase plasma proteins. Induction of enhanced net synthesis of fibrinogen, alpha1-acid glycoprotein, alpha2 (acute phase)-globulin, and haptoglobin by amino acids and hormones during perfusion of the isolated normal rat liver. J Biol Chem. 1969 Nov 25;244(22):6134–6142. [PubMed] [Google Scholar]
- Kampschmidt R. F., Upchurch H. F. Effect of leukocytic endogenous mediator on plasma fibrinogen and haptoglobin. Proc Soc Exp Biol Med. 1974 Jul;146(3):904–907. doi: 10.3181/00379727-146-38216. [DOI] [PubMed] [Google Scholar]
- Kampschmidt R. F., Upchurch H. F., Pulliam L. A. Characterization of a leukocyte-derived endogenous mediator responsible for increased plasma fibrinogen. Ann N Y Acad Sci. 1982;389:338–353. doi: 10.1111/j.1749-6632.1982.tb22148.x. [DOI] [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]
- Liang T. J., Grieninger G. Direct effect of insulin on the synthesis of specific plasma proteins: biphasic response of hepatocytes cultured in serum- and hormone-free medium. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6972–6976. doi: 10.1073/pnas.78.11.6972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MANS R. J., NOVELLI G. D. A convenient, rapid and sensitive method for measuring the incorporation of radioactive amino acids into protein. Biochem Biophys Res Commun. 1960 Nov;3:540–543. doi: 10.1016/0006-291x(60)90171-6. [DOI] [PubMed] [Google Scholar]
- Majumdar A. P., Jorgensen A. J. Influence of cortisol on tryptophan-mediated stimulation of hepatic protein synthesis in well-fed adrenalectomized rats. Biochem Med. 1977 Feb;17(1):116–119. doi: 10.1016/0006-2944(77)90014-x. [DOI] [PubMed] [Google Scholar]
- McKenzie J. M., Fowler P. R. Supporting role of the adrenal cortex in the induction of hyperfibrinogenemia. Am J Physiol. 1968 Apr;214(4):786–790. doi: 10.1152/ajplegacy.1968.214.4.786. [DOI] [PubMed] [Google Scholar]
- Nickerson J. M., Fuller G. M. In vitro synthesis of rat fibrinogen: identification of preA alpha, preB beta, and pre gamma polypeptides. Proc Natl Acad Sci U S A. 1981 Jan;78(1):303–307. doi: 10.1073/pnas.78.1.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Princen H. M., Selten G. C., Selten-Versteegen A. M., Mol-Backx G. P., Nieuwenhuizen W., Yap S. H. Distribution of mRNAS of fibrinogen polypeptides and albumin in free and membrane-bound polyribosomes and induction of alpha-fetoprotein mRNA synthesis during liver regeneration after partial hepatectomy. Biochim Biophys Acta. 1982 Nov 30;699(2):121–130. doi: 10.1016/0167-4781(82)90145-2. [DOI] [PubMed] [Google Scholar]
- Princen J. M., Mol-Backx G. P., Yap S. H. Acute effects of ethanol intake on albumin and total protein synthesis in free and membrane-bound polyribosomes of rat liver. Biochim Biophys Acta. 1981 Sep 28;655(2):119–127. doi: 10.1016/0005-2787(81)90001-0. [DOI] [PubMed] [Google Scholar]
- Princen J. M., Nieuwenhuizen W., Mol-Backx G. P., Yap S. H. Direct evidence of transcriptional control of fibrinogen and albumin synthesis in rat liver during the acute phase response. Biochem Biophys Res Commun. 1981 Sep 30;102(2):717–723. doi: 10.1016/s0006-291x(81)80191-x. [DOI] [PubMed] [Google Scholar]
- Ritchie D. G., Levy B. A., Adams M. A., Fuller G. M. Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1530–1534. doi: 10.1073/pnas.79.5.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seglen P. O. Preparation of isolated rat liver cells. Methods Cell Biol. 1976;13:29–83. doi: 10.1016/s0091-679x(08)61797-5. [DOI] [PubMed] [Google Scholar]
- Seligsohn U., Alexander N., Rapaport S. I. Fibrinogen synthesis in adrenalectomized rabbits. Proc Soc Exp Biol Med. 1973 Mar;142(3):824–828. doi: 10.3181/00379727-142-37125. [DOI] [PubMed] [Google Scholar]
- Selten G. C., Princen H. M., Selten-Versteegen A. M., Mol-Backx G. P., Yap S. H. Sequence content of alpha-fetoprotein, albumin and fibrinogen polypeptide mRNAs in different organs, developing tissues and in liver during carcinogenesis in rats. Biochim Biophys Acta. 1982 Nov 30;699(2):131–137. doi: 10.1016/0167-4781(82)90146-4. [DOI] [PubMed] [Google Scholar]
- Strair R. K., Yap S. H., Shafritz D. A. Use of molecular hybridization to purify and analyze albumin messenger RNA from rat liver. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4346–4350. doi: 10.1073/pnas.74.10.4346. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor J. M., Schimke R. T. Synthesis of rat liver albumin in a rabbit reticulocyte cell-free protein-synthesizing system. J Biol Chem. 1973 Nov 25;248(22):7661–7668. [PubMed] [Google Scholar]
- Van Ruijven-Vermeer I. A., Nieuwenhuizen W. Purification of rat fibrinogen and its constituent chains. Biochem J. 1978 Mar 1;169(3):653–658. doi: 10.1042/bj1690653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weimer H. E., Humelbaugh C. The effects of periodic challenge on the response of alpha-2-AP globulin and other acute-phase reactants of rat serum to tissue injury. Can J Physiol Pharmacol. 1967 Mar;45(2):241–247. doi: 10.1139/y67-027. [DOI] [PubMed] [Google Scholar]