Nutrition‐related alterations in liver microsomal testosterone hydroxylases

Abstract

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.

Modulation of rat liver peroxisomal and microsomal fatty acid oxidation by starvation

“…The nutritional status of animals modulates the liver microsomal metabolism of several endogenous compounds such as fatty acids and steroidal hormones [9]. Malnutrition selectively decreases all of the oxidation Abbrcvialions: co, 12-hydroxy laurie acid; w-l, 1 l-hydroxy laurie acid.…”

Nutritional requirements for detoxication of environmental chemicals

“…Fructose 1,6-diphosphate, a readily available source of ATP which can cross the cellular membrane barrier, increases liver ATP levels, polyamine synthesis, and hepatic regeneration, and decreases liver injury following administration of the hepatotoxic, lethal mixture of chlordecone plus carbon tetrachloride (Rao and Mehendale 1989). Nutrition, especially proteinenergy nutrition, also affects the activities of individual cytochromes P-450, a deficiency in calories enhancing the activities of P450 IIE1 and probably P450 IV (Hong et al 1987), while protein-energy malnourished rats show regioselective changes in the hydroxylation of endogenous substrates, such as testosterone (Gil et al 1988) and arachidonate, which affects the relative extents of formation of the various eicosanoids (Orellana et al 1989).…”