Inhibition of aromatase improves nutritional status following portacaval anastomosis in male rats.
OBJECTIVE
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 16alpha hydroxylase and 15beta 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 16alpha hydroxylase was lower and estradiol driven 15beta 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.
Dasarathy
Srinivasan
S
Gastroenterology Division, Department of Medicine, Metro Health Medical Center, Case Western Reserve University, Cleveland, OH, USA. sdasarathy@metrohealth.org
Mullen
Kevin D
KD
Dodig
Milan
M
Donofrio
Barbara
B
McCullough
Arthur J
AJ