This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shi, Y. E. Articles by Yager, J. D. Search for Related Content PubMed PubMed Citation Articles by Shi, Y. E. Articles by Yager, J. D.

Effects of the Liver Tumor Promoter Ethinyl Estradiol on Epidermal Growth Factor-induced DNA Synthesis and Epidermal Growth Factor Receptor Levels in Cultured Rat Hepatocytes¹

Departments of Biochemistry [Y. E. S.] and Anatomy [J. D. Y.], Dartmouth Medical School, Hanover, New Hampshire 03756

The objective of this study was to determine whether DNA synthesis induced in the livers of female rats treated with ethinyl estradiol (EE) was due to direct effects of this synthetic estrogen on hepatocytes. Hepatocytes, obtained by collagenase perfusion from female Lewis rats, were cultured in serum-free medium containing low or no phenol red and supplemented with insulin, transferrin, and selenium. When present at 10–15 µM for the initial 30 h of culture, EE caused a subsequent 2–2.7-fold increase in hepatocyte DNA synthesis. Pretreatment of the hepatocytes with EE during the first 30 h of culture caused an EE concentration-dependent enhancement of their subsequent DNA synthetic response to epidermal growth factor (EGF). Pretreatment with EE shifted the EGF dose-response curve, causing a dramatic enhancement of the response to EGF beginning at 2 ng EGF/ml. The response to a saturating (25 ng/ml) dose of EGF was also greatly enhanced. Determination of the effect of EE on hepatocyte surface EGF receptors revealed that the increased responsiveness of DNA synthesis to EGF was accompanied by a twofold increase in EGF receptor number per cell. These results indicate that EE has direct, growth-related effects on hepatocytes which may contribute to liver growth induced in vivo by this tumor promoter.

¹ Supported by Grant CA-36701. The Norris Cotton Cancer Center Support (CORE) Grant CA-23108 supported the use of shared services and equipment.

² Recipient of a Friends of the Norris Cotton Cancer Center Predoctoral Fellowship.

³ To whom requests for reprints should be addressed.

Received 4/ 7/88. Revised 3/27/89. Accepted 3/31/89.

This article has been cited by other articles:

				D. R. Boverhof, K. C. Fertuck, L. D. Burgoon, J. E. Eckel, C. Gennings, and T. R. Zacharewski Temporal- and dose-dependent hepatic gene expression changes in immature ovariectomized mice following exposure to ethynyl estradiol Carcinogenesis, July 1, 2004; 25(7): 1277 - 1291. [Abstract] [Full Text] [PDF]

				C. H. Lee and A. M. Edwards Stimulation of DNA synthesis and c-fos mRNA expression in primary rat hepatocytes by estrogens Carcinogenesis, September 1, 2001; 22(9): 1473 - 1481. [Abstract] [Full Text] [PDF]

				L. Klotz, H. J. Hacker, D. Klingmuller, P. Bannasch, U. Pfeifer, and F. Dombrowski Hepatocellular Alterations after Intraportal Transplantation of Ovarian Tissue in Ovariectomized Rats Am. J. Pathol., May 1, 2000; 156(5): 1613 - 1626. [Abstract] [Full Text] [PDF]