1. The hepatic CYP4A-dependent omega-hydroxylation of
arachidonic acid and CYP2C11-dependent 2alpha-/16alpha-hydroxylations of
testosterone were decreased to 74 and 60% of respective control in microsomal fractions from
vitamin A-deficient rats. Decreases in the rates of
arachidonic acid omega-1-hydroxylation and
testosterone 6beta-, 7alpha- and 17alpha-hydroxylations were less pronounced. 2. Corresponding decreases in microsomal
CYP4A and CYP2C11 immunoreactive
protein expression to 64 and 68% of respective control were observed in
vitamin A-deficient rat liver. Expression of
CYP3A proteins was unchanged from
vitamin A-adequate control. 3. Northern analysis revealed a selective decrease in
CYP4A2 mRNA expression in
vitamin A-deficient rat liver to approximately 5% of control; expression of the related CYP4A1/4A3 mRNAs was not decreased. CYP2C11
mRNA expression was also decreased in
vitamin A-deficient male rat liver to 39% of control levels. 4. Intake of the deficient diet containing
all-trans-retinoic acid (ATRA) during the final week of the experiment restored
CYP4A2 mRNA and
CYP4A protein. Administration of exogenous
androgen or episodic
growth hormone was ineffective. In contrast, CYP2C11 expression was restored by ATRA and
androgen, but not by
growth hormone. 5. From these studies it emerges that
CYP4A2, a
fatty acid omega-hydroxylase in rat liver, is highly dependent on
vitamin A for optimal expression, whereas CYP2C11 is indirectly down regulated by
androgen deficiency resulting from
vitamin A-deficiency. Altered CYP expression in
vitamin A-deficiency provides insights into the relationship between dietary constituents and the intracellular formation of vasoactive
eicosanoids as well as the clearance of androgenic
steroids.