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This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/E993    most recent 00037.2005v1 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 Web of Science 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 Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Shin, Y. Articles by Joles, J. A. Search for Related Content PubMed PubMed Citation Articles by Shin, Y. Articles by Joles, J. A.

Effects of gender on hepatic HMG-CoA reductase, cholesterol 7-hydroxylase, and LDL receptor in hereditary analbuminemia

¹Division of Nephrology and Hypertension, Departments of Medicine, Physiology and Biophysics, University of California, Irvine, California; and ²Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands

Submitted 28 January 2005 ; accepted in final form 15 July 2005

Hypoalbuminemia is accompanied by hypercholesterolemia in both nephrotic syndrome and hereditary analbuminemia. Hypercholesterolemia is more severe in the female than in the male Nagase analbuminemic rats (NAR). The sex difference in plasma cholesterol diminishes after ovariectomy (OVX) and reappears after estrogen replacement in the NAR. The molecular mechanism responsible for the sex difference in severity of hypercholesterolemia in NAR is not known and was investigated here. To this end, hepatic hydroxylmethylglutaryl (HMG)-CoA reductase, cholesterol 7-hydroxylase, and LDL receptor were determined in male, female, and OVX female NAR and Sprague-Dawley (SD) rats. Plasma cholesterol, triglycerides, and hepatic HMG-CoA reductase activities were greater in both female and male NAR than in SD rats. This was coupled with upregulation of cholesterol 7-hydroxylase in both male and female NAR compared with SD controls. LDL receptor in male NAR was similar to that in male SD rats but was significantly reduced in female NAR. OVX partially, but significantly, reduced plasma cholesterol and triglyceride levels in female NAR. This was coupled with a significant rise in hepatic cholesterol 7-hydroxylase and a modest increase in hepatic LDL receptor. In contrast, OVX resulted in a mild elevation of plasma cholesterol and no significant changes in total hepatic HMG-CoA reductase, cholesterol 7-hydroxylase, or LDL receptor in female SD rats. Thus the greater severity of hypercholesterolemia in the female NAR appears to be due, in part, to a combination of the constrained compensatory upregulation of cholesterol 7-hydroxylase and LDL receptor deficiency.

hyperlipidemia; hypercholesterolemia; nephrotic syndrome; proteinuria; low-density lipoprotein; hydroxymethylglutaryl-CoA reductase; bile acids

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