Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Antonio Francavilla, Brian I. Carr, Alessandro Azzarone, Lorenzo Polimeno, Ziqiu Wang, David H. Van Thiel, Vladimir Subbotin, John G. Prelich, Thomas E. Starzl

Research output: Contribution to journalArticle

Abstract

Subcutaneous injections of hormone triiodothyronine in rats resulted in peak blood levels at 24 hr with return to baseline by 96 hr. The injections stimulated a liver regeneration response that resembled in timing and in magnitude of DNA synthesis (peak, 24 hr) that induced by 40% hepatic resection. The principal proliferation was of hepatocytes. Although there were some temporal differences from the gene expression of transforming growth factor-α, transforming growth factor-β, and c-Ha-ras that are known to follow partial hepatectomy, the overall profile of these changes was similar to those after partial resection. The effect was liver specific and could be reproduced three times with no diminution in response in the same animal with injections at 10-day intervals. No response was detected in kidney or intestine. This effect in intact animals contrasted with the minimal ability of triiodothyronine to stimulate hepatocytes in culture. However, when the culture medium was enriched with epidermal growth factor, there was a dose-related response to triiodothyronine. The totality of these experiments provides a preliminary basis for the creation with pharmacological techniques of an in vivo hyperplastic hepatic condition permissive of transfection of new genes, as an alternative to partial hepatectomy. Although triiodothyronine was the test agent used, other hepatic growth factors singly or in combination could be candidates for this purpose.

Original languageEnglish
Pages (from-to)1237-1241
Number of pages5
JournalHepatology
Volume20
Issue number5
Publication statusPublished - Nov 1994

ASJC Scopus subject areas

  • Hepatology

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    Francavilla, A., Carr, B. I., Azzarone, A., Polimeno, L., Wang, Z., Van Thiel, D. H., Subbotin, V., Prelich, J. G., & Starzl, T. E. (1994). Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro. Hepatology, 20(5), 1237-1241.