Nutrition-related alterations in liver microsomal testosterone hydroxylases

The oxidation products of testosterone formed by liver microsomes from normal-fed and protein-energy malnourished male rats have been analysed by HPLC. Microsomes from normal-fed rats oxidized testosterone at a rate of 4.52 nmol/min/mg protein. The major products formed were: 6 beta-, 7 alpha- and 16-alpha-hydroxytestosterone; these three metabolites represented 65% of the total testosterone metabolism. Microsomes from protein-energy malnourished rats oxidized testosterone at a reduced rate of 2.03 nmol/min/mg protein. The major product formed was 7 alpha-hydroxytestosterone, which accounted for 43% of total testosterone oxidation. Microsomes from protein-energy malnourished rats showed a CO-reduced cytochrome P-450 spectra with a maxima at 452 nm, and a 38% decrease in the total content of cytochrome P-450. Some testosterone hydroxylases were drastically affected by protein-energy malnutrition but others, such as 7 alpha-hydroxylase, remained unchanged. The present results suggest that nutritional status can modify the relative amounts of individual cytochrome P-450 isozymes, thus explaining the observed changes in several testosterone hydroxylases. Protein-energy malnutrition seems to be an excellent tool with which to obtain a microsomal fraction containing predominantly P-450 isozymes, which are probably involved in key mono-oxygenations of physiological substrates.