JBC, Vol. 250, Issue 21, 8496-8502, Nov, 1975
Influence of cholesterol feeding on liver microsomal metabolism of steroids and bile acids in conventional and germ-free rats
B. E. Gustafsson, K. Einarsson and J. Gustafsson
The present investigation has aimed at defining the factor responsible for
the differences in microsomal metabolism of steroids between germ-free and
conventional rats. Cholesterol, cholic acid, taurocholic acid, and
chenodeoxycholic acid were fed to conventional and germ-free male rats and
the effects on liver microsomal metabolism of
4-[4-14C]androstene-3,17-dione,
5alpha-[4-14C]androstane-3alpha,17beta-diol, [4-14C]-cholesterol,
7alpha-hydroxy-4-[6beta-3H]cholesten-3-one, and [24-14C]lithocholic acid
were studied. The most consistent effects were found with dietary
cholesterol that stimulated the activities of several of the hydroxylases
active on 4-androstene-3,17-dione and 5alpha-androstane-3alpha,17beta-diol
and that decreased the 5alpha reduction of 4-androstene-3,17-dione,
increased the 7alpha hydroxylation of cholesterol, decreased the 12alpha
hydroxylation of 7alpha-hydroxy-4-cholesten-3-one, and increased by 6beta
hydroxylation of lithocholic acid. These effects of cholesterol feeding on
the microsomal metabolism of steroids in conventional rats made the pattern
of microsomal enzyme activities resemble that characteristic of germ-free
rats. Cholesterol feeding led to a pronounced increase in the intestinal
concentration of beta-muricholic acid in conventional rats. Furthermore,
cholesterol feeding to conventional animals led to an intestinal ratio of
chenodeoxycholic acid (including its metabolites alpha- and beta-muricholic
acid and hyodeoxycholic acid) to cholic acid (including deoxycholic acid)
that was almost identical to that in germ-free rats. Conventionalization of
germ-free rats for a period of up to 56 days led only to a partial
normalization of the liver microsomal metabolism of
5alpha-[4-14C]androstane-3alpha, 17beta-diol and
7alpha-hydroxy-4-[6beta-3H]cholesten-3-one and of the liver microsomal
concentration of cytochrome P-450. The concentration of cholesterol was
higher in both total liver homogenate and liver microsomal fraction of
germ-free rats than in corresponding preparations from conventional rats.
In conclusion, it is suggested that cholesterol is one of the factors
responsible for the different microsomal metabolism of steroids in
germ-free and conventional rats. It is also suggested that cholesterol may
play a role as regulator of microsomal enzyme activities.
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