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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Feb;81(3):974–978. doi: 10.1073/pnas.81.3.974

Quantitative investigation of hepatic genomic response to hormonal and pathophysiological stimuli by multivariate analysis of two-dimensional mRNA activity profiles.

F E Carr, C Bingham, J H Oppenheimer, C Kistner, C N Mariash
PMCID: PMC344962  PMID: 6366794

Abstract

We have applied techniques of multivariate analysis to the characterization and comparison of the effects of various pathophysiological and hormonal stimuli on the expression of the rat hepatic genome at a pretranslational level. In vitro translated products were resolved by two-dimensional gel electrophoresis. We analyzed 10 pathophysiological states brought about by variation in thyroidal status, starvation, administration of high carbohydrate diet, and the production of experimentally induced diabetes mellitus. Each state differed significantly from every other state in the two-dimensional electrophoretic profiles. The set consisting of the minimal number of products necessary for maintaining the distinctive patterns was identified. The analysis also defined those clusters of products that behaved in a coordinate fashion in response to the various stimuli. Lastly, the similarity and dissimilarity of hepatic mRNA activity profiles to each other could be geometrically represented in three-dimensional space. Our finding that the hepatic mRNA activity profile could distinguish reliably between closely related hormonal and pathophysiological stimuli indicates the specificity of hepatic genomic expression. A systematic analysis of such profiles may be useful as an overall index of the biologic response at the hepatocellular level.

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Selected References

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

  1. Carr F. E., Seelig S., Mariash C. N., Schwartz H. L., Oppenheimer J. H. Starvation and hypothyroidism exert an overlapping influence on rat hepatic messenger RNA activity profiles. J Clin Invest. 1983 Jul;72(1):154–163. doi: 10.1172/JCI110953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Liaw C., Seelig S., Mariash C. N., Oppenheimer J. H., Towle H. C. Interactions of thyroid hormone, growth hormone, and high carbohydrate, fat-free diet in regulating several rat liver messenger ribonucleic acid species. Biochemistry. 1983 Jan 4;22(1):213–221. doi: 10.1021/bi00270a031. [DOI] [PubMed] [Google Scholar]
  4. Mariash C. N., McSwigan C. R., Towle H. C., Schwartz H. L., Oppenheimer J. H. Glucose and triiodothyronine both induce malic enzyme in the rat hepatocyte culture: evidence that triiodothyronine multiplies a primary glucose-generated signal. J Clin Invest. 1981 Dec;68(6):1485–1490. doi: 10.1172/JCI110401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Mariash C. N., Seelig S., Oppenheimer J. H. A rapid, inexpensive, quantitative technique for the analysis of two-dimensional electrophoretograms. Anal Biochem. 1982 Apr;121(2):388–394. doi: 10.1016/0003-2697(82)90498-5. [DOI] [PubMed] [Google Scholar]
  6. Morrison M. R., Pardue S., Griffin W. S. Developmental alterations in the levels of translationally active messenger RNAs in the postnatal rat cerebellum. J Biol Chem. 1981 Apr 10;256(7):3550–3556. [PubMed] [Google Scholar]
  7. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  8. Oppenheimer J. H., Schwartz H. L. Factors determining the level of activity of 3,5,3'-triiodothyronine-responsive hepatic enzymes in the starved rat. Endocrinology. 1980 Nov;107(5):1460–1468. doi: 10.1210/endo-107-5-1460. [DOI] [PubMed] [Google Scholar]
  9. Savage M. J., Sala-Trepat J. M., Bonner J. Measurement of the complexity and diversity of poly(adenylic acid) containing messenger RNA from rat liver. Biochemistry. 1978 Feb 7;17(3):462–467. doi: 10.1021/bi00596a014. [DOI] [PubMed] [Google Scholar]
  10. Seelig S., Jump D. B., Towle H. C., Liaw C., Mariash C. N., Schwartz H. L., Oppenheimer J. H. Paradoxical effects of cycloheximide on the ultra-rapid induction of two hepatic mRNA sequences by triiodothyronine (T3). Endocrinology. 1982 Feb;110(2):671–673. doi: 10.1210/endo-110-2-671. [DOI] [PubMed] [Google Scholar]
  11. Seelig S., Liaw C., Towle H. C., Oppenheimer J. H. Thyroid hormone attenuates and augments hepatic gene expression at a pretranslational level. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4733–4737. doi: 10.1073/pnas.78.8.4733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Towle H. C., Mariash C. N., Oppenheimer J. H. Changes in the hepatic levels of messenger ribonucleic acid for malic enzyme during induction by thyroid hormone or diet. Biochemistry. 1980 Feb 5;19(3):579–585. doi: 10.1021/bi00544a029. [DOI] [PubMed] [Google Scholar]

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