Inhibition of aromatase improves nutritional status following portacaval anastomosis in male rats

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• 作者：Srinivasan Dasarathy ; Kevin D. Mullen ; Milan Dodig ; Barbara Donofrio and Arthur J. McCullough
• 刊名：Journal of Hepatology
• 出版年：2006
• 出版时间：August 2006
• 年：2006
• 卷：45
• 期：2
• 页码：214-220
• 全文大小：164 K

文摘

Background/Aims

The portacaval anastamosis (PCA) rat is a model of the nutritional and endocrine consequences of liver cirrhosis. We hypothesized that failure to gain body weight in the PCA rat was the consequence of low testosterone levels and will be reversed by 4-hydroxyandrostenedione, a specific aromatase inhibitor.

Methods

Male Sprague–Dawley rats subjected to an end-to-side PCA or sham surgery were administered either 4-hydroxyandrostenedione or vehicle. Food intake, food efficiency, and body weight were measured, animals sacrificed 3 weeks after surgery, visceral organs harvested and plasma sex steroids measured. Hepatic RNA was extracted and dot blots done to quantify the expression of sex hormone dependent enzymes 16α hydroxylase and 15β hydroxylase.

Results

Growth, food intake, food efficiency and plasma testosterone were lower and plasma estradiol higher in PCA than sham rats. Hepatic expression of testosterone driven 16α hydroxylase was lower and estradiol driven 15β hydroxylase higher in PCA rats. These alterations were reversed by 4-hydroxyandrostenedione.

Conclusions

These observations demonstrate that use of aromatase inhibitor reverses the nutritional and endocrine abnormalities in the PCA rat and suggest that this approach may be useful in cirrhotic patients.