HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koopen, N. R. Articles by Princen, H. M. G. Search for Related Content PubMed PubMed Citation Articles by Koopen, N. R. Articles by Princen, H. M. G. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 40, 100-108, January 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

Differential effects of 17-ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat

Correspondence to: Folkert Kuipers

Effects of 17-ethinylestradiol (EE) on the neutral and acidic biosynthetic pathways of bile salt (BS) synthesis were evaluated in rats with an intact enterohepatic circulation and in rats with long-term bile diversion to induce BS synthesis. For this purpose, bile salt pool composition, synthesis of individual BS in vivo, hepatic activities, and expression levels of cholesterol 7-hydroxylase (CYP7A), and sterol 27-hydroxylase (CYP27), as well as of other enzymes involved in BS synthesis, were analyzed in rats treated with EE (5 mg/kg, 3 days) or its vehicle. BS pool size was decreased by 27% but total BS synthesis was not affected by EE in intact rats. Synthesis of cholate was reduced by 68% in EE-treated rats, while that of chenodeoxycholate was increased by 60%. The recently identified ²²-isomer of ß-muricholate contributed for 5.4% and 18.3 % (P < 0.01) to the pool in control and EE-treated rats, respectively, but could not be detected in bile after exhaustion of the pool. A clear reduction of BS synthesis was found in bile-diverted rats treated with EE, yet biliary BS composition was only minimally affected. Activity of CYP7A was decreased by EE in both intact and bile-diverted rats, whereas the activity of the CYP27 was not affected. Hepatic mRNA levels of CYP7A were significantly reduced by EE in bile-diverted rats only; CYP27 mRNA levels were not affected by EE. In addition, mRNA levels of sterol 12-hydroxylase and lithocholate 6ß-hydroxylase were increased by bile diversion and suppressed by EE.

This study shows that 17-ethinylestradiol (EE)-induced intrahepatic cholestasis in rats is associated with selective inhibition of the neutral pathway of bile salt (BS) synthesis. Simultaneous impairment of other enzymes in the BS biosynthetic pathways may contribute to overall effects of EE on BS synthesis.—Koopen, N. R., S. M. Post, H. Wolters, R. Havinga, F. Stellaard, R. Boverhof, F. Kuipers, and H. M. G. Princen. Differential effects of 17-ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat. J. Lipid Res. 1999. 40: 100–108.

Supplementary key words: cholestasis, estrogens, bile, ²²-ß-muricholate, cholesterol-7-hydroxylase, sterol-27-hydroxylase, enterohepatic circulation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. L. Ruiz, S. S.M. Villanueva, M. G. Luquita, S.-i. Ikushiro, A. D. Mottino, and V. A. Catania Beneficial Effect of Spironolactone Administration on Ethynylestradiol-Induced Cholestasis in the Rat: Involvement of Up-Regulation of Multidrug Resistance-Associated Protein 2 Drug Metab. Dispos., November 1, 2007; 35(11): 2060 - 2066. [Abstract] [Full Text] [PDF]

				L. A. Henriquez-Hernandez, A. Flores-Morales, R. Santana-Farre, M. Axelson, P. Nilsson, G. Norstedt, and L. Fernandez-Perez Role of Pituitary Hormones on 17{alpha}-Ethinylestradiol-Induced Cholestasis in Rat J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 695 - 705. [Abstract] [Full Text] [PDF]

				Y. Yamamoto, R. Moore, H. A. Hess, G. L. Guo, F. J. Gonzalez, K. S. Korach, R. R. Maronpot, and M. Negishi Estrogen Receptor {alpha} Mediates 17{alpha}-Ethynylestradiol Causing Hepatotoxicity J. Biol. Chem., June 16, 2006; 281(24): 16625 - 16631. [Abstract] [Full Text] [PDF]

				F. A. Crocenzi, J. M. Pellegrino, V. A. Catania, M. G. Luquita, M. G. Roma, A. D. Mottino, and E. J. S. Pozzi GALACTOSAMINE PREVENTS ETHINYLESTRADIOL-INDUCED CHOLESTASIS Drug Metab. Dispos., June 1, 2006; 34(6): 993 - 997. [Abstract] [Full Text] [PDF]

				M. L. Ruiz, S. S. M. Villanueva, M. G. Luquita, M. Vore, A. D. Mottino, and V. A. Catania ETHYNYLESTRADIOL INCREASES EXPRESSION AND ACTIVITY OF RAT LIVER MRP3 Drug Metab. Dispos., June 1, 2006; 34(6): 1030 - 1034. [Abstract] [Full Text] [PDF]

				S. Fiorucci, C. Clerici, E. Antonelli, S. Orlandi, B. Goodwin, B. M. Sadeghpour, G. Sabatino, G. Russo, D. Castellani, T. M. Willson, et al. Protective Effects of 6-Ethyl Chenodeoxycholic Acid, a Farnesoid X Receptor Ligand, in Estrogen-Induced Cholestasis J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 604 - 612. [Abstract] [Full Text] [PDF]

				M. Schwarz, D. W. Russell, J. M. Dietschy, and S. D. Turley Alternate pathways of bile acid synthesis in the cholesterol 7{alpha}-hydroxylase knockout mouse are not upregulated by either cholesterol or cholestyramine feeding J. Lipid Res., October 1, 2001; 42(10): 1594 - 1603. [Abstract] [Full Text] [PDF]