Age and gender effect on the inducibility of steroid metabolizing cytochrome P450 in rat liver.
Liver microsomal steroid hydroxylases and 5 alpha reductase activities were evaluated by quantitation of specific metabolites from 4-C14 progesterone after TLC separation. Each enzyme showed a different developmental profile depending on the gender of the rat. Dexamethasone induced both 6 beta and 16 alpha progesterone hydroxylase, being more potent for 6 beta (3 to 4 folds) than 16 alpha (1.2 to 1.6 folds). A comparison of the inducibility of 6 beta and 16 alpha hydroxylase by dexamethasone in rats from different age groups showed that for both enzymes, the degree of increase was higher in the younger than older groups. Thus there is a blunting in the responsiveness to dexamethasone induction of both 6 beta and 16 alpha hydroxylase with age particularly in female animals. This decrease in responsiveness in older females could potentially affect their capacity to metabolize endogenous and exogenous agents.
Lee
P C
PC
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
Struve
M F
MF
Werlin
S L
SL
D000375:Aging / Q000378:metabolism*; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000378:metabolism*; D010088:Oxidoreductases; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D039181:Steroid 16-alpha-Hydroxylase
D007527:Isoenzymes; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019392:Cytochrome P-450 CYP2E1; D039181:Steroid 16-alpha-Hydroxylase; D042944:Cholestenone 5 alpha-Reductase